Bio

Clinical Focus


  • Bladder Cancer
  • Testicular Tumors - Medical Oncology
  • Cancer > Urologic Oncology
  • Kidney Cancer
  • Male Cancers - Prostate
  • Male Cancers - Penile
  • Male Cancers - Testicular
  • Penile Cancer
  • Medical Oncology
  • Urologic Cancers
  • Bladder Cancer - Medical Oncology
  • Germ Cell Tumors
  • Germ Cell Tumors - Urologic Oncology
  • Prostate Cancer - Medical Oncology
  • Urologic Cancers - Medical Oncology
  • Ureteral Cancer - Medical Oncology
  • Urethral Cancer
  • Kidney Cancer - Medical Oncology
  • Prostate Cancer
  • Oncology (Cancer)
  • Urethral Cancer - Medical Oncology
  • Ureteral Cancer
  • Testicular Tumors
  • Germ Cell Tumors - Medical Oncology

Academic Appointments


Administrative Appointments


  • Unit based Medical Director, Stanford Hospital (2012 - Present)
  • Prostate Panel member, NCCN (2002 - Present)
  • DSMC Vice Chair, Stanford University (2002 - Present)

Honors & Awards


  • Oncology Clinical Fellows Teaching award, Stanford University (2009)
  • Oncology Clinical Fellows Teaching award, Stanford University (2008)
  • Oncology Clinical Fellows teaching award, Stanford University (2007)
  • Oncology Clinical Fellows Teaching award, Stanford University (2006)
  • Oncology Clinical Fellows Teaching award, Stanford University (2005)
  • Oncology Clinical Fellows teaching award, Stanford University (2004)
  • Oncology clinical fellows teaching award, Stanford University (2003)
  • Medicine Chief residents teaching award, Stanford University (2003)
  • Oncology Teaching award, Stanford University (2002)

Professional Education


  • Residency:St Mary's Hospital - New York (1991) NY
  • Internship:St Mary's Hospital - New York (1991) NY
  • Board Certification: Medical Oncology, American Board of Internal Medicine (1997)
  • Medical Education:Madras University Medicine (1985) India
  • Fellowship:UCSF Medical Center (1994) CA

Research & Scholarship

Current Research and Scholarly Interests


The Genito-Urinary Multidisciplinary tumor board at Stanford specalizes in taking care of patients with prostate cancer, renal cancer, testicular and bladder cancer. Patients are seen at different stages of their tumor. A multisdiscplinary approach is used. A variety of clinical trials are available to patients. Phase II trials using unique combination of chemotherapy agents, antiangiogenic drugs, novel agents are being explored.Co-operative group particpation through ECOG is also available

Clinical Trials


  • Evaluating Sunitinib Therapy in Renal Cell Carcinoma Using F-18 FDG PET/CT and DCE MRI Not Recruiting

    To learn whether FDG PET/CT and DCE MRI are better predictors of response to therapy than the current standard of care (CT or MRI).

    Stanford is currently not accepting patients for this trial. For more information, please contact Andrew Quon, (650) 736 - 1369.

    View full details

  • Study of Cabozantinib (XL184) Versus Mitoxantrone Plus Prednisone in Men With Previously Treated Symptomatic Castration-resistant Prostate Cancer Recruiting

    Bone metastases and associated pain are a major cause of morbidity and mortality in castration-resistant prostate cancer (CRPC). Most approved therapies have shown some ability to reduce soft tissue lesions but none meaningfully impacts bone metastases (as demonstrated by lack of resolution of lesions on bone scan with these agents) or the pain associated with these metastases. This study will evaluate the effect of cabozantinib versus mitoxantrone plus prednisone on pain response and bone scan response in men with CRPC.

    View full details

  • Treatment of Refractory Metastatic Renal Cell Carcinoma With Bevacizumab and RADOO1 Not Recruiting

    To test whether using bevacizumab and RAD001 together to treat metastatic renal cell cancer is safe and effective.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sarah Barbeau, 650-723-6286.

    View full details

  • A Pilot Study Evaluating Oral Triamcinalone in Patients With Androgen Independent Prostate Cancer Not Recruiting

    The primary purpose of this study is to evaluate the ability of oral triamcinalone given twice a day to patients with androgen independent prostate cancer to produce a sustained biochemical response. Secondary goals are to describe the safety and tolerability at this dose and schedule, to determine the time to sustained biochemical response, to determine the duration of biochemical response, to determine the time to disease progression.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • A Phase II Trial of Calcitriol and Naproxen in Patients With Recurrent Prostate Cancer Not Recruiting

    To determine whether, in this patient population, treatment with calcitriol and Naproxen is more effective in delaying the growth of prostate cancer than treatment with calcitriol alone as seen in historical controls.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • A Trial of Thalidomide and Capecitabine in Metastatic Renal Cell Carcinoma Not Recruiting

    The purpose of this study is to determine the efficacy of the combination of thalidomide and capecitabine in metastatic renal cell carcinoma and also to determine the safety of the combination.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Provide Expanded Access to MDV3100 and Monitor Its Safety in Patients With Progressive Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Chemotherapy Not Recruiting

    The purpose of this treatment protocol is to provide expanded access to MDV3100 and monitor its safety in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel-based chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • A Registry of Sipuleucel-T Therapy in Men With Advanced Prostate Cancer Not Recruiting

    The purpose of this study is to further quantify the risk of cerebrovascular events (CVEs) following sipuleucel-T (PROVENGE®) therapy, and to follow all subjects for survival.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Aflibercept in Combination With Docetaxel in Metastatic Androgen Independent Prostate Cancer Not Recruiting

    Primary objective was to demonstrate overall survival improvement with aflibercept compared to placebo in patients receiving docetaxel / prednisone for metastatic androgen-independent prostate cancer (MAIPC). The secondary objectives were: - To assess the efficacy of aflibercept compared to placebo on other parameters such prostate-specific antigen (PSA) level, cancer related pain, progression free survival (PFS), tumor-based and skeletal events and health-related quality of life (HRQL); - To assess the overall safety in both treatment arms; - To determine the pharmacokinetics of intravenous (IV) aflibercept in this population; - to determine immunogenicity of IV aflibercept.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • MEDI-522 in the Treatment of Patients With Metastatic Androgen-Independent Prostate Cancer Not Recruiting

    The primary objectives of this study are: 1. To explore the antitumor activity of MEDI-522 in combination with docetaxel, prednisone, and zoledronic acid in patients with metastatic Androgen-Independent Prostate Cancer (AIPC); and 2. To summarize the safety of MEDI-522 in combination with docetaxel, prednisone, and zoledronic acid in this patient population.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • A Study Evaluating the Efficacy and Safety of Sunitinib With or Without Bevacizumab in First-Line Patients With Metastatic Renal Cell Cancer (SABRE-R) Not Recruiting

    This is a Phase II, multicenter, randomized, blinded, placebo-controlled study designed to evaluate the safety and efficacy of combining bevacizumab with sunitinib relative to placebo with sunitinib in patients with metastatic RCC who have not received prior systemic therapy for metastatic disease. The study will enroll approximately 100 patients at approximately 20 centers in the United States.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • TroVax® In Subjects With Hormone Refractory Prostate Cancer (HRPC) Not Recruiting

    Based on both pre-clinical and clinical data, it may be advantageous to administer a cancer vaccine before chemotherapy to enhance immune responses, thus leading to a more effective therapeutic approach for subjects with metastatic HRPC. This clinical study will evaluate the role of combination therapy of TroVax® plus Docetaxel vs. Docetaxel alone on the progression free survival (PFS) of subjects with HRPC.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer Recruiting

    This randomized phase III trial is studying gemcitabine hydrochloride, cisplatin, and bevacizumab to see how well they work compared with gemcitabine hydrochloride, cisplatin, and placebo in treating patients with advanced urinary tract cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether gemcitabine hydrochloride and cisplatin are more effective when given together with or without bevacizumab in treating patients with urinary tract cancer.

    View full details

  • A Phase 1b, Open-Label, Dose-Finding Study to Evaluate the Safety of Tivozanib (AV-951) in Combination With Temsirolimus in Subjects With Metastatic Renal Cell Carcinoma Not Recruiting

    The purpose of this study is to test the safety and tolerability of tivozanib (AV-951) and Torisel™ given in combination for renal cell cancer. The study will also assess the effects of the combination of tivozanib (AV-951) and Torisel™ on the tumor. Tivozanib (AV-951) is a VEGF-receptor tyrosine kinase inhibitor, and may stop the growth of tumor cells by blocking blood flow to the tumor. Temsirolimus is an mTOR inhibitor which is approved for the treatment of advanced renal cell carcinoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Safety and Toxicity Study of Sorafenib in Patients With Kidney Cancer Not Recruiting

    Objectives: Primary • Evaluate the safety and toxicity of dose escalating Sorafenib for patients with progressive metastatic renal cell carcinoma. Secondary: - To assess tumor responses produced by Sorafenib - To evaluate time to progression produced by Sorafenib - To assess overall survival Methodology: Open label, multi-center, dose escalation trial - Subject maximum dose administered will depend on observed subject tolerability - Subject escalation to next dose level will occur only after acceptable tolerance has been demonstrated by Subject

    Stanford is currently not accepting patients for this trial. For more information, please contact Haas Denise, (650) 736 - 1252.

    View full details

  • Zoledronic Acid With Intermittent Hormonal Therapy in Patients With Prostate Cancer Not Recruiting

    Primary: To determine the duration of use of zoledronic acid in improving Bone mineral density in patients with prostate cancer who are on hormones intermittently. Secondary Objectives: To describe the safety and tolerability at this dose and schedule

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • A Study of HSP90 Inhibitor AT13387 Alone or in Combination With Abiraterone Acetate Not Recruiting

    A 2-part, Phase 1-2, open-label, parallel group, randomized study in patients with Castration-Resistant Prostate Cancer (CRPC) who are no longer responding to treatment with abiraterone and steroids. In Part A (Phase 1), patients will continue to receive the same doses of abiraterone and steroids they were receiving prior to study entry and will be randomized to receive 1 of 2 different treatment regimens of AT13387 in combination with abiraterone. Once the best regimen is established in Part A, based on safety and antitumor activity, patients will be randomized to the selected treatment regimen and dose of AT13387 in combination with abiraterone or AT13387 alone in Part B (Phase 2).

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, 650-736-1252.

    View full details

  • A Phase II Study of AZD4877 (a Novel Anti-mitotic Agent) in Advanced Bladder Cancer Not Recruiting

    The purpose of this Phase II study is to determine if AZD4877, an experimental drug that is a novel anti-mitotic agent (Eg5 or Kinesin Spindle Protein inhibitor that interferes with tumor cell division leading to tumor growth), can reduce tumor sizes in patients with bladder cancer

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Sunitinib Malate or Sorafenib Tosylate in Treating Patients With Kidney Cancer That Was Removed By Surgery Not Recruiting

    This randomized phase III trial is studying sunitinib malate to see how well it works compared to sorafenib tosylate or placebo in treating patients with kidney cancer that has been removed by surgery. Sunitinib malate and sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib malate or sorafenib tosylate after surgery may kill any tumor cells that remain after surgery. It is not yet known whether sunitinib malate is more effective than sorafenib tosylate or placebo in treating kidney cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Tivantinib With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Locally Advanced Kidney Cancer That Cannot be Removed by Surgery Not Recruiting

    This randomized phase II trial studies how well tivantinib with or without erlotinib hydrochloride works in treating patients with metastatic or locally advanced kidney cancer that cannot be removed by surgery. Tivantinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    Stanford is currently not accepting patients for this trial. For more information, please contact Preeti Chavan, 650-725-0426.

    View full details

  • Sunitinib Malate With or Without Gemcitabine Hydrochloride in Treating Patients With Advanced Kidney Cancer That Cannot Be Removed By Surgery Recruiting

    RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth or tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving sunitinib malate and gemcitabine hydrochloride together is more effective than sunitinib malate alone in treating patients with kidney cancer. PURPOSE: This randomized phase II clinical trial is studying giving sunitinib malate together with or without gemcitabine hydrochloride to see how well they work in treating patients with advanced kidney cancer that cannot be removed by surgery.

    View full details

  • Bicalutamide With or Without Akt Inhibitor MK2206 in Treating Patients With Previously Treated Prostate Cancer Not Recruiting

    This phase II clinical trial is studying how well giving bicalutamide with or without Akt inhibitor MK2206 works in treating patients with previously treated prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of androgens made by the body. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether bicalutamide is more effective with or without Akt inhibitor MK2206 in treating prostate cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Preeti Chavan, 650-725-0426.

    View full details

  • A Phase 1b Study of SGN-75 in Combination With Everolimus in Patients With Renal Cell Carcinoma Not Recruiting

    This is a phase 1, open-label, dose-escalation clinical trial to evaluate the safety of SGN-75 in combination with everolimus in patients with CD70-positive metastatic renal cell carcinoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Abiraterone Acetate in Asymptomatic or Mildly Symptomatic Patients With Metastatic Castration-Resistant Prostate Cancer Not Recruiting

    This is a phase 3 study to compare the clinical benefit of abiraterone acetate plus prednisone with placebo plus prednisone in asymptomatic or mildly symptomatic patients with metastatic castration-resistant prostate cancer (CRPC).

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • A Phase II Study of GSK1363089 (Formerly XL880) for Papillary Renal-Cell Carcinoma (PRC) Not Recruiting

    This clinical study is being conducted at multiple sites to determine the best confirmed response rate, safety, and tolerability of GSK1363089 treatment in papillary renal cell carcinoma. Papillary renal cell carcinoma may be classified into hereditary and sporadic forms; subjects with either classification will be accepted into this study.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Probiotic Supplementation in Preventing Treatment-Related Diarrhea in Patients With Cancer Undergoing Chemotherapy Not Recruiting

    This randomized phase II clinical trial studies probiotic supplementation in preventing treatment-related diarrhea in patients with cancer undergoing chemotherapy. Probiotics may help prevent diarrhea caused by treatment with chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, 650-736-1252.

    View full details

  • A Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer Not Recruiting

    The purpose of this study is to determine the benefit of MDV3100 versus placebo as assessed by overall survival and progression-free survival in patients with progressive metastatic prostate cancer who have failed androgen deprivation therapy but not yet received chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sarah Barbeau, (650) 723 - 6286.

    View full details

  • A Rollover Protocol to Allow Continued Access to Tivozanib (AV 951) for Subjects Enrolled in Other Tivozanib Protocols Not Recruiting

    Open-label, multi-center, multi-national rollover study to allow continued access to tivozanib for subjects who have participated in other tivozanib (monotherapy or combination) protocols. Eligible subjects will continue to receive tivozanib at the same dose and schedule as per the original (parent) protocol. The length of time that a subject must be on the parent protocol before rolling over to this protocol will be dictated by the (original) parent protocol. Subjects will be seen by the investigator every 4 weeks (± 5 days). Adverse events and blood pressure will be recorded. At the beginning of Cycle 1 and at the beginning of every odd-numbered cycle (Cycle 3, Cycle 5, etc), clinical laboratory values will be recorded. CT scans to assess disease will be performed at the end of even-numbered cycles (Cycle 2, Cycle 4, etc).

    Stanford is currently not accepting patients for this trial. For more information, please contact Sarah Barbeau, (650) 723 - 6286.

    View full details

  • BMS-936558 (MDX-1106) In Subjects With Advanced/Metastatic Clear-Cell Renal Cell Carcinoma (RCC) Not Recruiting

    The purpose of this study is to measure how active BMS-936558 is against Renal Cell Carcinoma (RCC) as measured by the disease not progressing and whether a dose response relationship exists.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sarah Barbeau, (650) 723 - 6286.

    View full details

  • Fulvestrant in Hormone Refractory Prostate Cancer Not Recruiting

    The purpose of this study is to determine if treatment with fulvestrant leads to a slowing of tumor progression in patients who have developed androgen-independent (AIPC) or hormone-refractory prostate cancer (HRPC) and who have a rising serum prostate specific antigen (PSA).

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • A Randomized, Double-blind, Phase 3 Efficacy Trial of PROSTVAC-V/F +/- GM-CSF in Men With Asymptomatic or Minimally Symptomatic Metastatic Castrate-Resistant Prostate Cancer Recruiting

    The purpose of this study is to determine whether PROSTVAC alone or in combination with GM-CSF is effective in prolonging overall survival in men with few or no symptoms from metastatic, castrate-resistant prostate cancer.

    View full details

  • Study of Nivolumab (BMS-936558) vs. Everolimus in Pre-Treated Advanced or Metastatic Clear-cell Renal Cell Carcinoma (CheckMate 025) Not Recruiting

    The purpose of the study is to compare the clinical benefit, as measured by duration of overall survival, of Nivolumab vs. Everolimus in subjects with advanced or metastatic clear-cell renal cell carcinoma who have received prior anti-angiogenic therapy

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, 650-736-1252.

    View full details

  • AMG 102 in Combination With Mitoxantrone and Prednisone in Subjects With Previously Treated Castrate Resistant Prostate Cancer Not Recruiting

    The primary objectives of this study are the following: Phase 1b: To identify a safe dose level of AMG 102, up to 15 mg/kg Q3W, to combine with mitoxantrone and prednisone (MP) Phase 2: To estimate with adequate precision the effect of the addition of AMG 102 to MP, compared with placebo plus MP, as assessed by the hazard ratio (HR) for overall survival (OS) of previously treated subjects with castrate-resistant prostate cancer (CRPC)

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Adjuvant Taxotere in Patients With High Risk Prostate Cancer Post Prostatectomy and Radiation Not Recruiting

    The purpose of this study is to evaluate time to progression (TTP) by PSA in patients with high risk prostate cancer after definitive therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • F18PET/CT Versus TC-MDP Scanning to Detect Bone Mets Not Recruiting

    The primary objective is to compare the diagnostic performance of 18F- Fluoride PET/CT scanning to that of conventional bone scanning for detecting cancer that has spread to the bone (bone metastasis). The intent of the study is to determine whether 18F-Fluoride PET/CT will lead to improved treatment and patient outcomes.

    Stanford is currently not accepting patients for this trial. For more information, please contact Andrei Iagaru, (650) 736 - 2859.

    View full details

  • Study of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma Not Recruiting

    This study will evaluate the safety and efficacy of Dovitinib versus sorafenib in patients with metastatic renal cell cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sarah Barbeau, (650) 723 - 6286.

    View full details

  • Study of AS1404 With Docetaxel in Patients With Hormone Refractory Metastatic Prostate Cancer Not Recruiting

    The purpose of this trial is to confirm a safe dose of AS1404, to be given with docetaxel, and to see whether adding AS1404 and docetaxel together improves the outcome of the treatment, when compared to docetaxel alone.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ruth Lira, (650) 723 - 1367.

    View full details

  • DN24-02 as Adjuvant Therapy in Subjects With High Risk HER2+ Urothelial Carcinoma Not Recruiting

    This study is being conducted to examine survival, safety, and the magnitude of the immune response induced following administration of DN24-02 in subjects with HER2+ urothelial carcinoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Study of Gemcitabine and Cisplatin With or Without Cetuximab in Urothelial Cancer Not Recruiting

    This study will compare the effects, good and/or bad, of chemotherapy (Gemcitabine and Cisplatin) with or without the addition of the chemotherapy drug Cetuximab to find out which treatment is better.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • A Study of CDX-1127 in Patients With Select Solid Tumor Types or Hematologic Cancers Recruiting

    This is a study of CDX-1127, a therapy that targets the immune system and may act to promote anti-cancer effects. The study enrolls patients with hematologic cancers (certain leukemias and lymphomas), as well as patients with select types of solid tumors.

    View full details

  • Study of Abiraterone Acetate in Patients With Advanced Prostate Cancer Not Recruiting

    The purpose of this study is to collect additional safety information on abiraterone acetate administered with prednisone to patients with metastatic castration-resistant prostate cancer (CRPC).

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Safety and Efficacy Study of Enzalutamide Versus Bicalutamide in Men With Prostate Cancer Not Recruiting

    The purpose of this study is to determine the safety and efficacy of enzalutamide vs. bicalutamide in asymptomatic or mildly symptomatic patients with prostate cancer who have disease progression despite primary androgen deprivation therapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sarah Barbeau, (650) 723 - 6286.

    View full details

  • Study of Itraconazole in Castration Resistant Prostate Cancer (CRPC) Post Docetaxel Chemotherapy Not Recruiting

    Assess the efficacy of itraconazole as an anticancer drug in CRPC as measured by a drop in serum PSA

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Radium-223 Dichloride (BAY88-8223) in Castration-Resistant (Hormone-Refractory) Prostate Cancer Patients With Bone Metastases Recruiting

    This study is a prospective, interventional, open-label, multi-center early access program for the use of Ra-223 Cl2 in HRPC/CRPC patients diagnosed with symptomatic bone metastasis and to collect additional short and long term safety data on the product.

    View full details

  • Phase II GM-CSF Plus Mitoxantrone in Hormone Refractory Prostate Cancer Not Recruiting

    The purpose of this study is to evaluate the effect of the combination of mitoxantrone and GM-CSF on time to progression in patients with hormone-refractory prostate cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • A Study to Evaluate Pazopanib as an Adjuvant Treatment for Localized Renal Cell Carcinoma (RCC) Not Recruiting

    This randomized Phase III study is to evaluate whether pazopanib compared with placebo can prevent or delay recurrence of kidney cancer in patients with moderately high or high risk of developing recurrence after undergoing kidney cancer surgery

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, 650736-1252.

    View full details

  • Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer Not Recruiting

    There is a clear need for novel effective agents in castration-resistant prostate cancer (CRPC), an entity previously referred to as "androgen-insensitive" or "hormone-refractory" prostate cancer. While numerous therapies impact biochemical response in this disease, none improve overall survival outside of chemotherapy. The mechanisms behind progression to castration-resistance are unclear, but preclinical studies suggest that loss of the tumor suppressor gene PTEN and subsequent up-regulation of Akt, which is upstream of mTOR, may be involved in prostate cancer progression and metastasis. Based on these observations, we hypothesize that inhibition of mTOR activity with an IV mTOR inhibitor, temsirolimus, may prolong hormone sensitivity and delay disease progression. We have received approval and drug support from the NCCN and Wyeth to study temsirolimus in castration-resistant prostate cancer before antiandrogen withdrawal in a phase II, single stage, non-randomized clinical trial. Forty patients who are currently on combined androgen blockade with bicalutamide, who have evidence of disease progression by PSA or bony metastasis will receive temsirolimus weekly for 13 weeks. Because evaluating new therapies in prostate cancer is uniquely challenging given its long natural history and relatively indolent nature, this study will employ an established surrogate endpoint for efficacy, prostate-specific antigen (PSA), which will permit preliminary evaluation of this combination in fewer patients and in less time than would otherwise be possible in this disease, and additionally evaluates secondary time-to-event outcomes. By co-targeting the androgen and PTEN/Akt/mTOR signaling pathways in castration-resistant prostate cancer, we see great potential to impact this pervasive disease.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • A Phase 2 Study to Investigate the Clinical Activity of IPI-504 in Patients With Hormone-resistant Prostate Cancer Not Recruiting

    To determine: - Anti-tumor activity of IPI-504 in 2 groups of subjects with hormone resistant prostate cancer. - Group A - subjects who have not previously received chemotherapy - Group B - sujects who have received prior chemotherapy or could not tolerate chemotherapy. - Clinical response will be determined by PSA and radiological response

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Study to Evaluate Safety and Effectiveness of Lenalidomide in Combination With Docetaxel and Prednisone for Patients With Castrate-Resistant Prostate Cancer Not Recruiting

    The purpose of the study is to determine whether lenalidomide is safe and effective for use in combination with docetaxel and prednisone for the treatment of subjects with metastatic Castrate-Resistant Prostate Cancer. The addition of lenalidomide to docetaxel and prednisone is proposed to increase the life expectancy of these subjects.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Treatment Protocol for the Use of Sorafenib in Patients With Advanced Renal Cell Carcinoma Not Recruiting

    This treatment protocol allows doctors to treat advanced kidney cancer with an investigational drug called sorafenib, BAY43-9006, which is being studied in clinical trials for kidney cancer and other kinds of cancer. This treatment protocol is not a clinical trial in which sorafenib is compared to another equal treatment. All patients in this protocol will be treated with sorafenib. In addition, data from the patients who participate in this protocol will provide additional information about the drug.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Calcitriol or Placebo in Men for Prostate Cancer Active Surveillance Not Recruiting

    After the diagnosis of prostate cancer, many men alter their lifestyle or diet or use various supplements in an attempt to retard the growth of their cancer. While there is limited data on the use of diet and supplements to alter the risk of prostate cancer, even less is known regarding the ability of diet or supplements to alter progression. For men who have elected active surveillance, the investigators propose to investigate the ability of vitamin D to retard the growth of prostate cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office CCTO, (650) 498 - 7061.

    View full details

  • Phase I Sodium Selenite in Combination With Docetaxel in Castration-resistant Prostate Cancer Not Recruiting

    Selenium, in the form of inorganic Sodium Selenite, may be useful for treating existing prostate cancer. This idea is based on data from our laboratory showing that 1) prostate cancer cells are more sensitive to Selenium (Sodium Selenite)-induced apoptosis than normal prostate epithelial cells, 2) Selenite induces significant growth inhibition of well established prostate cancer tumors in mice at doses that have no detectable toxicity, and 3) Selenite disrupts AR signaling, and that the inhibition of AR expression and activity by Selenite occurs via a redox mechanism involving GSH, superoxide, and Sp1. Altogether, these findings suggest that Selenium may be useful in a variety of potential indications in the natural history of prostate cancer, including both hormone sensitive and castrate resistant prostate cancer, as a single agent, or in combination with radiation, chemotherapy or conventional hormone therapy. Selenite is a potential novel inhibitor of AR expression and function in prostate cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Phase 2 Trial of Enzastaurin in Prostate Cancer in Patients Who Have Had Hormonal and Chemotherapy Not Recruiting

    The purpose is to see how quickly two different types of prostate cancer patients respond when taking enzastaurin. Cohort 1 - asymptomatic patients with androgen-independent PSA-progressive disease with or without clinical or radiographic evidence of metastatic disease. Cohort 2 - patients with androgen-independent metastatic prostate cancer (documented bone or soft tissue metastases) with rising PSA, clinical, radiographic disease progression following one prior docetaxel-based regimen

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • First-Line Treatment of Advanced Bladder Cancer Randomized vs. Gemcitabine ± Vinflunine in Patients Ineligible to Receive Cisplatin-Based Therapy Not Recruiting

    The purpose of this study is to test an investigational drug, vinflunine (BMS-710485), in combination with gemcitabine in patients with Transitional Cell Carcinoma who cannot be treated with cisplatin. This study will help to determine whether vinflunine in combination with gemcitabine will extend the time period until further growth of the tumor more than gemcitabine alone.

    Stanford is currently not accepting patients for this trial. For more information, please contact Denise Haas, (650) 736 - 1252.

    View full details

  • Phase II Pazopanib in Combination With Weekly Paclitaxel in Refractory Urothelial Cancer Recruiting

    Based on the results from the Phase 1 study of pazopanib combined with paclitaxel and the activity of paclitaxel in urothelial cancer, testing this regimen in a disease where there is an unmet need appears appropriate.

    View full details

Teaching

2013-14 Courses


Publications

Journal Articles


  • Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials. Annals of oncology Heng, D. Y., Choueiri, T. K., Rini, B. I., Lee, J., Yuasa, T., Pal, S. K., Srinivas, S., Bjarnason, G. A., Knox, J. J., MacKenzie, M., Vaishampayan, U. N., Tan, M. H., Rha, S. Y., Donskov, F., Agarwal, N., Kollmannsberger, C., North, S., Wood, L. A. 2014; 25 (1): 149-154

    Abstract

    Targeted therapies in metastatic renal cell carcinoma (mRCC) have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of patients treated with targeted agents but are ineligible for trials are unknown.mRCC patients treated with vascular endothelial growth factor-targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky performance status (KPS) <70%, nonclear-cell histology, brain metastases, hemoglobin ≤9 g/dl, creatinine >2× the upper limit of normal, corrected calcium ≥12 mg/dl, platelet count of <100 × 10(3)/uL, or neutrophil count <1500/mm(3).Overall, 768 of 2210 (35%) patients in the International Metastatic RCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression-free survival (PFS) and median overall survival of first-line targeted therapy were 22% versus 29% (P = 0.0005), 5.2 versus 8.6 months, and 12.5 versus 28.4 months (both P < 0.0001), respectively. Second-line PFS (if applicable) was 2.8 months in the trial ineligible versus 4.3 months in the trial eligible patients (P = 0.0039). When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.55 (95% confidence interval 1.378-1.751, P < 0.0001).The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.

    View details for DOI 10.1093/annonc/mdt492

    View details for PubMedID 24356626

  • Prostate Cancer, Version 1.2014 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Mohler, J. L., Kantoff, P. W., Armstrong, A. J., Bahnson, R. R., Cohen, M., D'Amico, A. V., Eastham, J. A., Enke, C. A., Farrington, T. A., Higano, C. S., Horwitz, E. M., Kawachi, M. H., Kuettel, M., Lee, R. J., MacVicar, G. R., Malcolm, A. W., Miller, D., Plimack, E. R., Pow-Sang, J. M., Richey, S., Roach, M., Rohren, E., Rosenfeld, S., Small, E. J., Srinivas, S., Stein, C., Strope, S. A., Tward, J., Walsh, P. C., Shead, D. A., Ho, M. 2013; 11 (12): 1471-1479
  • Prostate cancer, version 1.2014. Journal of the National Comprehensive Cancer Network Mohler, J. L., Kantoff, P. W., Armstrong, A. J., Bahnson, R. R., Cohen, M., D'Amico, A. V., Eastham, J. A., Enke, C. A., Farrington, T. A., Higano, C. S., Horwitz, E. M., Kawachi, M. H., Kuettel, M., Lee, R. J., MacVicar, G. R., Malcolm, A. W., Miller, D., Plimack, E. R., Pow-Sang, J. M., Richey, S., Roach, M., Rohren, E., Rosenfeld, S., Small, E. J., Srinivas, S., Stein, C., Strope, S. A., Tward, J., Walsh, P. C., Shead, D. A., Ho, M. 2013; 11 (12): 1471-1479

    Abstract

    The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations on the clinical management of patients with prostate cancer. This report highlights notable recent updates. Radium-223 dichloride is a first-in-class radiopharmaceutical that recently received approval for the treatment of patients with symptomatic bone metastases and no known visceral disease. It received a category 1 recommendation as both a first-line and second-line option. The NCCN Prostate Cancer Panel also revised recommendations on the choice of intermittent or continuous androgen deprivation therapy based on recent phase III clinical data comparing the 2 strategies in the nonmetastatic and metastatic settings.

    View details for PubMedID 24335682

  • Metastatic non-clear cell renal cell carcinoma treated with targeted therapy agents: Characterization of survival outcome and application of the International mRCC Database Consortium criteria CANCER Kroeger, N., Xie, W., Lee, J., Bjarnason, G. A., Knox, J. J., Mackenzie, M. J., Wood, L., Srinivas, S., Vaishamayan, U. N., Rha, S., Pal, S. K., Yuasa, T., Donskov, F., Agarwal, N., Kollmannsberger, C. K., Tan, M., North, S. A., Rini, B. I., Choueiri, T. K., Heng, D. Y. 2013; 119 (16): 2999-3006

    Abstract

    This study aimed to apply the International mRCC Database Consortium (IMDC) prognostic model in metastatic non-clear cell renal cell carcinoma (nccRCC). In addition, the survival outcome of metastatic nccRCC patients was characterized.Data on 2215 patients (1963 with clear-cell RCC [ccRCC] and 252 with nccRCC) treated with first-line VEGF- and mTOR-targeted therapies were collected from the IMDC. Time to treatment failure (TTF) and overall survival (OS) were compared in groups with favorable, intermediate, and poor prognoses according to IMDC prognostic criteriaThe median OS of the entire cohort was 20.9 months. nccRCC patients were younger (P < .0001) and more often presented with low hemoglobin (P = .014) and elevated neutrophils (P = .0001), but otherwise had clinicopathological features similar to those of ccRCC patients. OS (12.8 vs 22.3 months; P < .0001) and TTF (4.2 vs 7.8 months; P < .0001) were worse in nccRCC patients compared with ccRCC patients. The hazard ratio for death and TTF when adjusted for the prognostic factors was 1.41 (95% CI, 1.19-1.67; P < .0001) and 1.54 (95% CI, 1.33-1.79; P < .0001), respectively. The IMDC prognostic model reliably discriminated 3 risk groups to predict OS and TTF in nccRCC; the median OS of the favorable, intermediate, and poor prognosis groups was 31.4, 16.1, and 5.1 months, respectively (P < .0001), and the median TTF was 9.6, 4.9, and 2.1 months, respectively (P < .0001).Although targeted agents have significantly improved the outcome of patients with nccRCC, for the majority survival is still inferior compared with patients with ccRCC. The IMDC prognostic model reliably predicts OS and TTF in nccRCC and ccRCC patients. Cancer 2013;119:2999-3006. © 2013 American Cancer Society.

    View details for DOI 10.1002/cncr.28151

    View details for Web of Science ID 000322632400011

    View details for PubMedID 23696129

  • A randomized, double-blind, placebo-controlled, Phase II study with and without enzastaurin in combination with docetaxel-based chemotherapy in patients with castration-resistant metastatic prostate cancer INVESTIGATIONAL NEW DRUGS Dreicer, R., Garcia, J., Rini, B., Vogelzang, N., Srinivas, S., Somer, B., Shi, P., Kania, M., Raghavan, D. 2013; 31 (4): 1044-1050

    Abstract

    Enzastaurin is an oral serine/threonine kinase inhibitor that inhibits the beta isoform of protein kinase C and which may have therapeutic activity in prostate cancer. We explored the efficacy of docetaxel/prednisone with or without enzastaurin in patients with castration-resistant metastatic prostate cancer.A nonrandomized safety cohort consisting of 14 patients was followed by a double-blind randomized Phase II trial. Patients received standard doses of docetaxel (75 mg/m(2)) with prednisone 10 mg daily with or without 500 mg/day of enzastaurin.There was no difference in the objective response rate between the enzastaurin and placebo arms (placebo: 7 [15.2 %]; enzastaurin: 6 [15.0 %]; P = 1.00). The median PFS was 229 days for patients in the enzastaurin arm versus 213 days for the placebo arm (P = 0.524). The 1-year overall survival rates were almost identical, with 76.7 % and 75.1 % in the enzastaurin and placebo arms, respectively. Therapy was well tolerated although the combination of enzastaurin and docetaxel was more myelosuppressive than with docetaxel alone.The clinical activity of docetaxel/prednisone plus enzastaurin cannot be distinguished from docetaxel/prednisone alone, given the limitations of a randomized Phase II design. Although the toxicity profile was favorable for the enzastaurin-containing regimen, there is no compelling rationale to move this combination forward for the treatment of castration-resistant metastatic prostate cancer.

    View details for DOI 10.1007/s10637-013-9940-0

    View details for Web of Science ID 000322333600026

    View details for PubMedID 23435622

  • A Phase II Study of Bevacizumab and Everolimus as Treatment for Refractory Metastatic Renal Cell Carcinoma. Clinical genitourinary cancer Harshman, L. C., Barbeau, S., McMillian, A., Srinivas, S. 2013; 11 (2): 100-106

    Abstract

    Agents that inhibit the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways in metastatic renal cell carcinoma (mRCC) prolong progression-free survival (PFS), but durable complete responses are rare. Combinations of these cytostatic therapies have great potential to improve efficacy and to escape tumoral resistance mechanisms, but supra-additive toxicity is a valid concern. We investigated whether horizontal blockade with the combination of bevacizumab, a monoclonal antibody to VEGF-A, and of everolimus, an oral mTOR inhibitor, improved PFS in patients with clear cell mRCC who had received prior VEGF blockade.In this phase II investigator-initiated study, 10 of 30 planned patients were enrolled. Bevacizumab 10 mg/kg was administered intravenously every 14 days. Everolimus was orally dosed at 10 mg daily. The patients were treated until disease progression or unacceptable toxicity. The primary endpoint was PFS.The median age was 55 years. The majority of patients were white men with an Eastern Cooperative Oncology Group performance status of 1 (80%) and intermediate risk disease by Memorial Sloan-Kettering Cancer Center criteria (70%). All the patients had received 1 prior VEGF inhibitor. The median PFS in the 10 evaluable patients was 5.1 months, which was less than the expected historical control of bevacizumab monotherapy at 6 months. The median overall survival was 21 months. The best response was a partial response in 1 patient and stable disease in 9. Forty percent of the patients were discontinued from the study due to toxicity.In our experience, the combination of bevacizumab and everolimus was toxic. The efficacy achieved did not support its combined use over sequential administration. Ongoing randomized studies will definitively evaluate the combination's efficacy and tolerability.

    View details for DOI 10.1016/j.clgc.2012.12.002

    View details for PubMedID 23352238

  • Surgical outcomes and complications associated with presurgical tyrosine kinase inhibition for advanced renal cell carcinoma (RCC) UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Harshman, L. C., Yu, R. J., Allen, G. I., Srinivas, S., Gill, H. S., Chung, B. I. 2013; 31 (3): 379-385

    Abstract

    Tyrosine kinase inhibitors (TKI) have dramatically changed the management paradigm of advanced renal cell carcinoma (RCC) and are increasingly being used preoperatively to achieve cytoreduction.To review our case series of post-TKI surgical procedures to add to the current perioperative efficacy and complication profile.Between October 2006 and February 2010, 14 cytoreductive nephrectomies, radical nephrectomies, and metastectomies were performed after neoadjuvant sunitinib or sorafenib for advanced RCC. During the same time frame, a control group of 73 consecutive patients underwent radical nephrectomy, cytoreductive nephrectomy, or metastectomy in the absence of prior systemic therapy. We compared the incidence of perioperative complications and outcomes after surgical procedures between the two cohorts.Median preoperative renal mass size was 11 cm (6.7-24.2 cm). Primary tumor shrinkage was seen in 57%; median shrinkage was 18% (8%-25%). The median treatment period was 17 weeks, and the median time from TKI discontinuation was 2 weeks. Compared with a control group and after adjusting for confounding covariates, presurgical TKI use was not associated with a significant increase in perioperative complications (50% vs. 40%, P = 0.25) or perioperative bleeding (36% vs. 34%, P = 0.97) but was associated with increased incidence and grade of intraoperative adhesions (86% vs. 58%, P = 0.001; grade 3 vs. 1, P = 0.002).Compared with the published reports, we observed less hemorrhagic and wound healing issues but a significant increase in incidence and severity of intraoperative adhesions, which can present a formidable technical challenge. Potential reasons for our lower complication rate could be increased time from TKI discontinuation to surgery, longer time to postoperative TKI re-initiation, increased use of preoperative angioembolization, and the lack of preoperative bevacizumab administration. Presurgical TKI therapy can permit effective surgical cytoreduction with a safety and complication profile equivalent to that of non-TKI-nephrectomy; however safety data continue to evolve, and preoperative TKI use requires further prospective investigation.

    View details for DOI 10.1016/j.urolonc.2011.01.005

    View details for Web of Science ID 000317169500015

    View details for PubMedID 21353796

  • Cabozantinib in Patients With Advanced Prostate Cancer: Results of a Phase II Randomized Discontinuation Trial JOURNAL OF CLINICAL ONCOLOGY Smith, D. C., Smith, M. R., Sweeney, C., Elfiky, A. A., Logothetis, C., Corn, P. G., Vogelzang, N. J., Small, E. J., Harzstark, A. L., Gordon, M. S., Vaishampayan, U. N., Haas, N. B., Spira, A. I., Lara, P. N., Lin, C., Srinivas, S., Sella, A., Schoeffski, P., Scheffold, C., Weitzman, A. L., Hussain, M. 2013; 31 (4): 412-419

    Abstract

    Cabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2. We evaluated the activity of cabozantinib in patients with castration-resistant prostate cancer (CRPC) in a phase II randomized discontinuation trial with an expansion cohort.Patients received 100 mg of cabozantinib daily. Those with stable disease per RECIST at 12 weeks were randomly assigned to cabozantinib or placebo. Primary end points were objective response rate at 12 weeks and progression-free survival (PFS) after random assignment.One hundred seventy-one men with CRPC were enrolled. Random assignment was halted early based on the observed activity of cabozantinib. Seventy-two percent of patients had regression in soft tissue lesions, whereas 68% of evaluable patients had improvement on bone scan, including complete resolution in 12%. The objective response rate at 12 weeks was 5%, with stable disease in 75% of patients. Thirty-one patients with stable disease at week 12 were randomly assigned. Median PFS was 23.9 weeks (95% CI, 10.7 to 62.4 weeks) with cabozantinib and 5.9 weeks (95% CI, 5.4 to 6.6 weeks) with placebo (hazard ratio, 0.12; P < .001). Serum total alkaline phosphatase and plasma cross-linked C-terminal telopeptide of type I collagen were reduced by ? 50% in 57% of evaluable patients. On retrospective review, bone pain improved in 67% of evaluable patients, with a decrease in narcotic use in 56%. The most common grade 3 adverse events were fatigue (16%), hypertension (12%), and hand-foot syndrome (8%).Cabozantinib has clinical activity in men with CRPC, including reduction of soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use.

    View details for DOI 10.1200/JCO.2012.45.0494

    View details for Web of Science ID 000314099800007

    View details for PubMedID 23169517

  • Phase II and Biomarker Study of the Dual MET/VEGFR2 Inhibitor Foretinib in Patients With Papillary Renal Cell Carcinoma JOURNAL OF CLINICAL ONCOLOGY Choueiri, T. K., Vaishampayan, U., Rosenberg, J. E., Logan, T. F., Harzstark, A. L., Bukowski, R. M., Rini, B. I., Srinivas, S., Stein, M. N., Adams, L. M., Ottesen, L. H., Laubscher, K. H., Sherman, L., McDermott, D. F., Haas, N. B., Flaherty, K. T., Ross, R., Eisenberg, P., Meltzer, P. S., Merino, M. J., Bottaro, D. P., Linehan, W. M., Srinivasan, R. 2013; 31 (2): 181-186

    Abstract

    Foretinib is an oral multikinase inhibitor targeting MET, VEGF, RON, AXL, and TIE-2 receptors. Activating mutations or amplifications in MET have been described in patients with papillary renal cell carcinoma (PRCC). We aimed to evaluate the efficacy and safety of foretinib in patients with PRCC.Patients were enrolled onto the study in two cohorts with different dosing schedules of foretinib: cohort A, 240 mg once per day on days 1 through 5 every 14 days (intermittent arm); cohort B, 80 mg daily (daily dosing arm). Patients were stratified on the basis of MET pathway activation (germline or somatic MET mutation, MET [7q31] amplification, or gain of chromosome 7). The primary end point was overall response rate (ORR).Overall, 74 patients were enrolled, with 37 in each dosing cohort. ORR by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was 13.5%, median progression-free survival was 9.3 months, and median overall survival was not reached. The presence of a germline MET mutation was highly predictive of a response (five of 10 v five of 57 patients with and without germline MET mutations, respectively). The most frequent adverse events of any grade associated with foretinib were fatigue, hypertension, gastrointestinal toxicities, and nonfatal pulmonary emboli.Foretinib demonstrated activity in patients with advanced PRCC with a manageable toxicity profile and a high response rate in patients with germline MET mutations.

    View details for DOI 10.1200/JCO.2012.43.3383

    View details for Web of Science ID 000313345100010

    View details for PubMedID 23213094

  • Targeted MET Inhibition in Castration-Resistant Prostate Cancer: A Randomized Phase II Study and Biomarker Analysis with Rilotumumab plus Mitoxantrone and Prednisone CLINICAL CANCER RESEARCH Ryan, C. J., Rosenthal, M., Ng, S., Alumkal, J., Picus, J., Gravis, G., Fizazi, K., Forget, F., Machiels, J., Srinivas, S., Zhu, M., Tang, R., Oliner, K. S., Jiang, Y., Loh, E., Dubey, S., Gerritsen, W. R. 2013; 19 (1): 215-224

    Abstract

    To evaluate the efficacy, safety, biomarkers, and pharmacokinetics of rilotumumab, a fully human, monoclonal antibody against hepatocyte growth factor (HGF)/scatter factor, combined with mitoxantrone and prednisone (MP) in patients with castration-resistant prostate cancer (CRPC).This double-blinded phase II study randomized (1:1:1) patients with progressive, taxane-refractory CRPC to receive MP (12 mg/m(2) i.v. day 1, 5 mg twice a day orally days 1-21, respectively) plus 15 mg/kg rilotumumab, 7.5 mg/kg rilotumumab, or placebo (i.v. day 1) every 3 weeks. The primary endpoint was overall survival (OS).One hundred and forty-four patients were randomized. Median OS was 12.2 versus 11.1 months [HR, 1.10; 80% confidence interval (CI), 0.82-1.48] in the combined rilotumumab versus control arms. Median progression-free survival was 3.0 versus 2.9 months (HR, 1.02; 80% CI, 0.79-1.31). Treatment appeared well tolerated with peripheral edema (24% vs. 8%) being more common with rilotumumab. A trend toward unfavorable OS was observed in patients with high tumor MET expression regardless of treatment. Soluble MET levels increased in all treatment arms. Total HGF levels increased in the rilotumumab arms. Rilotumumab showed linear pharmacokinetics when co-administered with MP.Rilotumumab plus MP had manageable toxicities and showed no efficacy improvements in this estimation study. High tumor MET expression may identify patients with CRPC with poorer prognosis.

    View details for DOI 10.1158/1078-0432.CCR-12-2605

    View details for Web of Science ID 000313051100023

    View details for PubMedID 23136195

  • mRNA-Seq of Single Prostate Cancer Circulating Tumor Cells Reveals Recapitulation of Gene Expression and Pathways Found in Prostate Cancer PLOS ONE Cann, G. M., Gulzar, Z. G., Cooper, S., Li, R., Luo, S., Tat, M., Stuart, S., Schroth, G., Srinivas, S., Ronaghi, M., Brooks, J. D., Talasaz, A. H. 2012; 7 (11)

    Abstract

    Circulating tumor cells (CTC) mediate metastatic spread of many solid tumors and enumeration of CTCs is currently used as a prognostic indicator of survival in metastatic prostate cancer patients. Some evidence suggests that it is possible to derive additional information about tumors from expression analysis of CTCs, but the technical difficulty of isolating and analyzing individual CTCs has limited progress in this area. To assess the ability of a new generation of MagSweeper to isolate intact CTCs for downstream analysis, we performed mRNA-Seq on single CTCs isolated from the blood of patients with metastatic prostate cancer and on single prostate cancer cell line LNCaP cells spiked into the blood of healthy donors. We found that the MagSweeper effectively isolated CTCs with a capture efficiency that matched the CellSearch platform. However, unlike CellSearch, the MagSweeper facilitates isolation of individual live CTCs without contaminating leukocytes. Importantly, mRNA-Seq analysis showed that the MagSweeper isolation process did not have a discernible impact on the transcriptional profile of single LNCaPs isolated from spiked human blood, suggesting that any perturbations caused by the MagSweeper process on the transcriptional signature of isolated cells are modest. Although the RNA from patient CTCs showed signs of significant degradation, consistent with reports of short half-lives and apoptosis amongst CTCs, transcriptional signatures of prostate tissue and of cancer were readily detectable with single CTC mRNA-Seq. These results demonstrate that the MagSweeper provides access to intact CTCs and that these CTCs can potentially supply clinically relevant information.

    View details for DOI 10.1371/journal.pone.0049144

    View details for Web of Science ID 000311935800219

    View details for PubMedID 23145101

  • Variations in Normal Serum Alpha-Fetoprotein (AFP) Levels in Patients with Testicular Cancer on Surveillance ONKOLOGIE Patel, P., Balise, R., Srinivas, S. 2012; 35 (10): 588-591

    Abstract

    The aim of this study was to assess fluctuations in normal serum alpha-fetoprotein (AFP) levels in patients with germ cell cancer. Marked variations occur after serum AFP levels normalize, creating anxiety among patients and physicians during surveillance.We conducted a retrospective review of patients with germ cell tumors in clinical remission, who had normal AFP levels and were followed at our center from 1991 to 2009. 72 patients, with a median follow-up of 50 months, were identified.Of the 72 patients, 57 (79%) had a non-seminomatous germ cell histology, and 15 (21%) had seminomas. Seminomas were included as controls as serum AFP levels do not increase in this group. 68 patients underwent orchiectomy, and 50 patients received systemic chemotherapy. The majority of patients (93%) demonstrated fluctuations in serum AFP. There was no difference in the mean AFP values between patients with seminona (2.95 ng/ml) and those with non-seminomatous germ cell tumors (3.3 ng/ml) (standard deviation 1.01 ng/ml).Marked variations occur after serum AFP levels normalize in patients undergoing surveillance. Fluctuating AFP levels within normal limits did not result in relapse in our cohort of patients with extended follow-up.

    View details for DOI 10.1159/000342695

    View details for Web of Science ID 000309666500007

    View details for PubMedID 23038230

  • Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy: a population-based study LANCET ONCOLOGY Harshman, L. C., Xie, W., Bjarnason, G. A., Knox, J. J., MacKenzie, M., Wood, L., Srinivas, S., Vaishampayan, U. N., Tan, M., Rha, S., Donskov, F., Agarwal, N., Kollmannsberger, C., North, S., Rini, B. I., Heng, D. Y., Choueiri, T. K. 2012; 13 (9): 927-935

    Abstract

    The advent of targeted therapies in the past 7 years has extended median survival for metastatic renal-cell carcinoma. This improvement in clinical outcome has created a need for new, more accurate prognostic measures. We assessed the use of conditional survival--a measure that accounts for elapsed time since treatment initiation--for prognostication in patients with metastatic renal-cell carcinoma treated with first-line VEGF-targeted therapies.We obtained data for patients with metastatic renal-cell carcinoma who were treated with a first-line VEGF-targeted therapy between April 7, 2003, and Oct 12, 2010, from our large multi-institutional International mRCC Database Consortium (centres in Canada, the USA, Singapore, Denmark, and South Korea). All histologies, performance statuses, and prognostic risk groups were included. The primary outcome was 2-year conditional survival, defined as the probability of surviving an additional 2 years from a given timepoint since the start of targeted therapy. Secondary analyses included 1-year and 3-year conditional survival, along with stratification of patients by Heng prognostic risk criteria and Karnofsky performance score, and conditional survival based on length of time on therapy. We used the Kaplan-Meier method and a landmark analysis to calculate conditional survival.In the 1673 patients analysed, median follow-up for alive patients was 20·1 months (IQR 9·0-34·4). We recorded an increase in the 2-year conditional survival probability from 44% (95% CI 41-47) at 0 months to 51% (46-55) at 18 months since beginning targeted therapy. When stratified by the Heng prognostic risk criteria defined at therapy initiation, 2-year conditional survival changed little in the favourable and intermediate groups, but in the poor-risk group, 2-year conditional survival improved from 11% (8-15) at 0 months to 33% (18-48) after 18 months. When conditioned on time on targeted therapy from 0 months to 18 months, 2-year conditional survival improved from 44% (41-47) to 68% (60-75) in the overall population and from 74% (68-79) to 90% (77-96) in the favourable group, 49% (45-53) to 57% (45-67) in the intermediate group, and 11% (8-15) to 73% (43-89) in the poor risk group.Conditional survival is a clinically useful prediction measure that adjusts prognosis of patients with metastatic renal-cell carcinoma on the basis of survival since treatment initiation or therapy duration. Conditional survival might be especially relevant to adjust prognosis for poor-risk patients.The Trust Family Fund for Kidney Cancer Research.

    View details for DOI 10.1016/S1470-2045(12)70285-1

    View details for Web of Science ID 000308425600020

    View details for PubMedID 22877847

  • Prostate Cancer, Version 3.2012 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Mohler, J. L., Armstrong, A. J., Bahnson, R. R., Boston, B., Busby, J. E., D'Amico, A. V., Eastham, J. A., Enke, C. A., Farrington, T., Higano, C. S., Horwitz, E. M., Kantoff, P. W., Kawachi, M. H., Kuettel, M., Lee, R. J., MacVicar, G. R., Malcolm, A. W., Miller, D., Plimack, E. R., Pow-Sang, J. M., Roach, M., Rohren, E., Rosenfeld, S., Srinivas, S., Strope, S. A., Tward, J., Twardowski, P., Walsh, P. C., Ho, M., Shead, D. A. 2012; 10 (9): 1081-1087

    Abstract

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer provide multidisciplinary recommendations for the clinical management of patients with prostate cancer. These NCCN Guidelines Insights highlight notable recent updates. Abiraterone acetate is a first-in-class hormonal agent that represents a new standard of care for patients with metastatic castration-recurrent prostate cancer who have previously received docetaxel (category 1 recommendation). Abiraterone acetate also received category 2B recommendations in the prechemotherapy setting for asymptomatic patients or symptomatic patients who are not candidates for docetaxel. The NCCN Prostate Cancer Panel also added new indications for existing agents, including the option of sipuleucel-T as second-line therapy. In addition, brachytherapy in combination with external beam radiation therapy with or without androgen deprivation therapy is now an alternative for patients with high-risk localized tumors or locally advanced disease.

    View details for Web of Science ID 000308575200006

    View details for PubMedID 22956807

  • Oral enzastaurin in prostate cancer: A two-cohort phase II trial in patients with PSA progression in the non-metastatic castrate state and following docetaxel-based chemotherapy for castrate metastatic disease INVESTIGATIONAL NEW DRUGS Dreicer, R., Garcia, J., Hussain, M., Rini, B., Vogelzang, N., Srinivas, S., Somer, B., Zhao, Y. D., Kania, M., Raghavan, D. 2011; 29 (6): 1441-1448

    Abstract

    Enzastaurin is an oral serine/threonine kinase inhibitor of the beta isoform of protein kinase C that may have therapeutic activity in prostate cancer. We explored the efficacy of enzastaurin on two cohorts of patients with prostate cancer progression in the castrate state.A two-cohort phase II trial was conducted, with both groups participating simultaneously. Cohort 1 consisted of patients with non-metastatic castrate prostate-specific antigen progressive disease. Cohort 2 consisted of patients with castrate metastatic disease with progression following docetaxel-based chemotherapy. Patients in both cohorts received 500 mg/day enzastaurin.Therapy was well tolerated in both cohorts. One complete response was observed in Cohort 1, with limited activity in the majority of patients. In Cohort 2, no objective responses were seen and the median progression-free survival (11 weeks [90% confidence interval: 7.6, 11.7]) did not differ from the historical control.Enzastaurin as a single agent has limited activity in castrate progressive prostate cancer. Evaluation in combination with docetaxel is ongoing.

    View details for DOI 10.1007/s10637-010-9428-0

    View details for Web of Science ID 000294824200035

    View details for PubMedID 20369375

  • Multicenter Phase II Trial of the Heat Shock Protein 90 Inhibitor, Retaspimycin Hydrochloride (IPI-504), in Patients With Castration-resistant Prostate Cancer UROLOGY Oh, W. K., Galsky, M. D., Stadler, W. M., Srinivas, S., Chu, F., Bubley, G., Goddard, J., Dunbar, J., Ross, R. W. 2011; 78 (3): 626-630

    Abstract

    To evaluate clinical activity and safety of retaspimycin hydrochloride (IPI-504) in patients with castration-resistant prostate cancer (CRPC).A single-arm trial was conducted in 2 cohorts: group 1, chemotherapy naive; group 2, docetaxel-treated. IPI-504 was administered intravenously at 400 mg/m2 on days 1, 4, 8, and 11 of a 21-day cycle. Trial expansion was planned if ?1 prostate-specific antigen (PSA) or radiographic response was noted per cohort. Pharmacokinetic samples were collected after the first dose; safety was assessed throughout.A total of 19 patients were enrolled (4 in group 1; 15 in group 2), with a median age of 66 years (range 49-78). Group 2 had received a median of 2 previous chemotherapy regimens. All group 2 patients had bone metastases; 66% had measurable soft tissue or visceral metastases. One group 1 patient remained on-trial for 9 cycles; his PSA level declined 48% from baseline. No PSA response was observed in the other patients. Adverse events reported in >25% of the study population included nausea (47%), diarrhea (42%), fatigue (32%), anorexia (26%), and arthralgia (26%). Two patients in group 2 died on-trial, involving study drug-related events of hepatic failure and ketoacidosis, respectively.Heat shock protein 90 inhibition with IPI-504 administered as a single agent had a minimal effect on the PSA level or tumor burden and was associated with unacceptable toxicity in several patients. Therefore, additional evaluation in CRPC patients is not warranted. IPI-504 is being investigated at less-intensive doses and schedules in other tumor types.

    View details for DOI 10.1016/j.urology.2011.04.041

    View details for Web of Science ID 000294483300049

    View details for PubMedID 21762967

  • Toxicities of targeted agents in advanced renal cell carcinoma. Current clinical pharmacology Patel, P., Srinivas, S. 2011; 6 (3): 181-188

    Abstract

    The targeted therapies available to treat metastatic kidney cancer include vascular endothelial growth factor (VEGF) inhibitors, bevacizumab, sorafenib, sunitinib, pazopanib, and the mTor inhibitors temsirolimus and everolimus. These agents have significantly improved patient outcomes but are associated with toxicities. The most common toxicities seen with the VEGF inhibitors are hypertension, fatigue, and hand- foot syndrome. The mTor inhibitors exhibit a different toxicity profile which includes hyperglycemia and hypertriglyceridemia. Recognition and understanding the mechanism of the toxicities is crucial for optimal patient management.

    View details for PubMedID 21827392

  • Pyoderma Gangrenosum With the Use of Sunitinib JOURNAL OF CLINICAL ONCOLOGY Nadauld, L. D., Miller, M. B., Srinivas, S. 2011; 29 (10): E266-E267

    View details for DOI 10.1200/JCO.2010.32.6165

    View details for Web of Science ID 000288990100005

    View details for PubMedID 21220606

  • NCCN Task Force Report: Optimizing Treatment of Advanced Renal Cell Carcinoma With Molecular Targeted Therapy J Natl Compr Canc Network Hudes GR, Carducci MA, Choueiri TK, Esper P, Jonasch E, KumarR, Margolin KA, Michaelson D, Motzer RJ, Pili P, Roethke S, Srinivas S 2011; 9: 29
  • Ribonucleotide reductase subunit M1 expression in resectable, muscle-invasive urothelial cancer correlates with survival in younger patients BJU INTERNATIONAL Harshman, L. C., Bepler, G., Zheng, Z., Higgins, J. P., Allen, G. I., Srinivas, S. 2010; 106 (11): 1805-1811

    Abstract

    To assess whether high ribonucleotide reductase subunit M1 (RRM1) expression in patients with resected, muscle-invasive (T2-4NxM0) urothelial carcinoma (UC) correlated with longer overall survival (OS). RRM1 is the primary cellular target of gemcitabine and previous studies in resected early-stage lung cancer have shown a survival benefit for patients with high expression.In all, 84 radical cystectomy specimens with muscle-invasive UC were identified from existing tissue microarrays. The patients' medical records were retrospectively reviewed to confirm pathology and stage. Specimens were analysed for RRM1 expression using automated quantitative analysis. The median value of RRM1 was established a priori as the threshold for high and low expression.The median age of the patients was 69 years. Stages were nearly equally distributed: 30%, 38%, and 32% for stage II, III, and IV, respectively. Most were high grade (99%) with no nodal involvement (69%). The median (range) OS was 2.0?(0-13.1) years. Tumoral RRM1 levels did not correlate with OS for the entire cohort, but when adjusted for age, high tumoral RRM1 expression in younger patients (aged <70 years) correlated with increased survival. Younger patients with high RRM1 expression had a median OS of 10.6 years compared with 1.6 years in older patients (P= 0.001). There was no difference in OS among low RRM1 expressors: 2.3 vs 1.6 years in younger and older patients, respectively (P= 0.22).Our results suggest that high RRM1 expression may be prognostic for improved survival in patients with muscle-invasive UC aged <70 years.

    View details for DOI 10.1111/j.1464-410X.2010.09327.x

    View details for Web of Science ID 000284275200049

    View details for PubMedID 20438561

  • Phase II Study on the Addition of ASA404 (Vadimezan; 5,6-Dimethylxanthenone-4-Acetic Acid) to Docetaxel in CRMPC CLINICAL CANCER RESEARCH Pili, R., Rosenthal, M. A., Mainwaring, P. N., van Hazel, G., Srinivas, S., Dreicer, R., Goel, S., Leach, J., Wong, S., Clingan, P. 2010; 16 (10): 2906-2914

    Abstract

    This randomized phase II study evaluated ASA404 (vadimezan; 5,6-dimethylxanthenone-4-acetic acid) in combination with docetaxel in castration-refractory metastatic prostate cancer (CRMPC).Seventy-four patients with histopathologically confirmed CRMPC previously untreated with chemotherapy were randomized to receive either

    View details for DOI 10.1158/1078-0432.CCR-09-3026

    View details for Web of Science ID 000278597600023

    View details for PubMedID 20460477

  • Prostate Cancer JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Mohler, J., Bahnson, R. R., Boston, B., Busby, J. E., D'Amico, A., Eastham, J. A., Enke, C. A., George, D., Horwitz, E. M., Huben, R. P., Kantoff, P., Kawachi, M., Kuettel, M., Lange, P. H., MacVicar, G., Plimack, E. R., Pow-Sang, J. M., Roach, M., Rohren, E., Roth, B. J., Shrieve, D. C., Smith, M. R., Srinivas, S., Twardowski, P., Walsh, P. C. 2010; 8 (2): 162-200
  • The bevacizumab experience in advanced renal cell carcinoma ONCOTARGETS AND THERAPY Harshman, L. C., Srinivas, S. 2010; 3: 179-189

    Abstract

    Bevacizumab in combination with interferon alfa is now approved for treatment-naïve advanced renal cell carcinoma (RCC) in both the US and Europe. Its objective response rates of 30% and progression-free survival rates of 9-10 months are comparable to the other approved first-line multityrosine kinase inhibitors, sunitinib and pazopanib. Its advantages include a different toxicity profile and assurance of administration compliance given its intravenous formulation. Enthusiasm for its use is blunted by the increased costs, the potential infusion-related reactions, the associated interferon-related toxicities, and the inconvenience of its nonoral formulation. Further study is warranted to assess its efficacy both as a single agent and in combination with the targeted agents and other immunotherapies. With multiple agents now available for the treatment of advanced RCC, identification of patient and tumor-specific biomarkers to inform our choice of first-line therapy and the proper sequence of subsequent therapies is imperative.

    View details for Web of Science ID 000286671700001

    View details for PubMedID 21049084

  • Adjuvant Docetaxel and androgen deprivation therapy in patients with High Risk Prostate Cancer Open Prostate Cancer Journal Bazan JG, King CR, Brooks JD, Srinivas S 2010; 3: 99-104
  • Phase II Study of Sunitinib Administered in a Continuous Once-Daily Dosing Regimen in Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma JOURNAL OF CLINICAL ONCOLOGY Escudier, B., Roigas, J., Gillessen, S., Harmenberg, U., Srinivas, S., Mulder, S. F., Fountzilas, G., Peschel, C., Flodgren, P., Maneval, E. C., Chen, I., Vogelzang, N. J. 2009; 27 (25): 4068-4075

    Abstract

    Sunitinib has demonstrated antitumor activity in metastatic renal cell carcinoma (mRCC) when given at 50 mg/d on a 4-weeks-on 2-weeks-off regimen. Herein, we report results of an open-label, multicenter phase II mRCC study of sunitinib administered on a continuous once-daily dosing regimen.Eligibility criteria included histologically proven mRCC with measurable disease, failure of one prior cytokine regimen, and good performance status. Patients were randomly assigned to a sunitinib starting dose of 37.5 mg/d in the morning (AM) or evening (PM). RECIST-defined objective response rate (ORR) was the primary end point. Secondary end points included progression-free survival (PFS), overall survival (OS), adverse events (AEs), and quality-of-life measures.One hundred seven patients were randomly assigned to AM (n = 54) or PM (n = 53) dosing and on study for a median 8.3 months. Eighty-three patients discontinued, 65 due to disease progression and 16 because of AEs; two patients withdrew consent. Dosing was reduced to 25 mg/d in 46 patients (43%) due to grade 3/4 AEs. The most common grade 3 treatment-related AEs were asthenia/fatigue (16%), diarrhea (11%), hypertension (11%), hand-foot syndrome (9%), and anorexia (8%). ORR was 20% with a 7.2-month median response duration. Median PFS and OS were 8.2 and 19.8 months, respectively, at median follow-up of 26.4 months. Efficacy, tolerability, and quality-of-life results were similar between patients dosed in the AM or PM.Sunitinib 37.5 mg, administered on a continuous once-daily dosing regimen, has a manageable safety profile as second-line mRCC therapy, providing flexible dosing, which can be explored in combination studies.

    View details for DOI 10.1200/JCO.2008.20.5476

    View details for Web of Science ID 000269381100008

    View details for PubMedID 19652072

  • A Phase II Trial of Calcitriol and Naproxen in Recurrent Prostate Cancer ANTICANCER RESEARCH Srinivas, S., Feldman, D. 2009; 29 (9): 3605-3610

    Abstract

    Androgen-deprivation therapy is commonly used in patients with progressive prostate cancer (PCa), but can be associated with unpleasant side-effects. The objective of the study was to determine whether treatment with calcitriol and naproxen is effective in safely delaying the growth and progression of PCa in men with early recurrent disease.Patients with biochemical relapse after local therapy for prostate cancer were treated with high dose calcitriol (DN101, Novacea) (45 microg once per week) and naproxen (375 mg twice daily) for one year and followed with serum PSA levels as well as imaging studies.Twenty-one patients were enrolled in the trial. Four patients met criteria for progression, with a PSA doubling time (PSADT) that decreased while on therapy. Fourteen patients had a prolongation of PSADT compared to baseline.Combination therapy with weekly calcitriol and daily naproxen is well tolerated by most patients and prolongation of PSADT was achieved in 75% of patients.

    View details for Web of Science ID 000268846900016

    View details for PubMedID 19667155

  • Laparoscopic radical nephrectomy after shrinkage of a caval tumor thrombus with sunitinib NATURE REVIEWS UROLOGY Harshman, L. C., Srinivas, S., Kamaya, A., Chung, B. I. 2009; 6 (6): 338-343

    Abstract

    A 57-year-old woman presented to the emergency department at a community hospital with a 2-month history of fatigue and right-sided flank and abdominal pain. Noncontrast CT of the abdomen and pelvis revealed a 9.1 cm right renal mass.Contrast CT of the chest, abdomen and pelvis, MRI of the abdomen and pelvis with gadolinium, radionuclide bone scan, lung nodule biopsy, complete blood count, comprehensive metabolic profile, and measurement of serum lactate dehydrogenase.Stage IV, T3bN0M1 clear cell renal cell carcinoma, with an associated tumor thrombus extending into the vena cava.The patient was treated with neoadjuvant sunitinib, which resulted in a marked response in the primary tumor and metastatic lesions as well as regression of the tumor thrombus well into the renal vein. Thus, laparoscopic radical nephrectomy was feasible and was achieved without hemorrhagic or wound healing complications. One month after surgery, she had evidence of disease progression in the lung and a periaortic lymph node. She was restarted on sunitinib with resultant disease stabilization, but discontinued the drug owing to toxicity. Eight months after cessation of sunitinib, she received a dendritic cell vaccine. She remains alive without evidence of disease progression 2 years after her diagnosis.

    View details for DOI 10.1038/nrurol.2009.84

    View details for Web of Science ID 000266773900012

    View details for PubMedID 19498412

  • Combination therapy with calcitriol and non-steroidal anti-inflammatory drugs in the treatment of prostate cancer Dermato Endocrinolgy Krishnan AV, Srinivas S, Feldman D 2009; 1: 7-11
  • A Phase II Study of Docetaxel and Oxaliplatin for Second-Line Treatment of Urothelial Carcinoma CHEMOTHERAPY Srinivas, S., Harshman, L. C. 2009; 55 (5): 321-326

    Abstract

    Despite high response rates with front-line platinum-based therapies, 80% of patients with metastatic urothelial cancer progress. Multiple agents and couplets have been investigated, but no standard second-line regimen exists. We conducted a phase II study to evaluate the efficacy and safety of docetaxel and oxaliplatin in metastatic urothelial cancer patients who had received prior platinum therapy.Patients with metastatic urothelial cancer, who had disease progression after platinum therapy, were treated with docetaxel 75 mg/m(2) and oxaliplatin 85 mg/m(2) every 3 weeks until disease progression or intolerable toxicity.Between November 2004 and September 2005, 11 patients were enrolled. All patients had low or intermediate Bajorin risk. The median number of cycles administered was 2 (range 2-8). One patient achieved near complete response. Three patients experienced disease stabilization, resulting in a disease-control rate of 36%. Median overall survival was 7 months. The most common toxicities were fatigue and anemia (50%).Second-line docetaxel and oxaliplatin in metastatic urothelial cancer is safe and tolerable but did not achieve an appreciable response rate.

    View details for DOI 10.1159/000230695

    View details for Web of Science ID 000270361800004

    View details for PubMedID 19641314

  • Increased Hemoglobin Associated with VEGF Inhibitors in Advanced Renal Cell Carcinoma CANCER INVESTIGATION Harshman, L. C., Kuo, C. J., Wong, B. Y., Vogelzang, N. J., Srinivas, S. 2009; 27 (8): 851-856

    Abstract

    We retrospectively analyzed whether increased hemoglobin is a surrogate biomarker of efficacy for vascular endothelial growth factor (VEGF) inhibitors in advanced renal cell carcinoma (RCC) patients. Twelve patients were identified who had received bevacizumab alone or as combination therapy. Eleven patients experienced a rise in hemoglobin. Median change was 1.6 g/dL (0-4.0). Degree of peak increase correlated with longer progression-free survival (PFS) in metastatic patients: increase of < 15% yielded a 3.1-month median PFS compared to 8.2 months with rises > 15%. This study identifies increased hemoglobin as a possible consequence of VEGF inhibitors. The correlation with longer PFS suggests that rise in hemoglobin may be a surrogate biomarker of efficacy.

    View details for DOI 10.1080/07357900902744528

    View details for Web of Science ID 000269542600007

    View details for PubMedID 19603304

  • High dose chemotherapy followed by stem cell rescue for high risk germ cell tumors: the Stanford experience. Bone Marrow Transplant Agarwal R, Dvorak CC, Stockerl- Goldstein KE, Johnson L, Srinivas S 2009; 43 (7): 547-52
  • Inhibition of prostaglandin synthesis and actions contributes to the beneficial effects of calcitriol in prostate cancer. Dermato-endocrinology Krishnan, A. V., Srinivas, S., Feldman, D. 2009; 1 (1): 7-11

    Abstract

    Our research is aimed at obtaining a better understanding of the molecular mechanisms of the anti-proliferative and cancer preventive effects of calcitriol with the goal of developing strategies to improve the treatment of prostate cancer (PCa). In PCa cells calcitriol inhibits the synthesis and biological actions of prostaglandins (PGs) by three actions: (i) the inhibition of the expression of cyclooxygenase-2 (COX-2), the enzyme that synthesizes PGs, (ii) the upregulation of the expression of 15-prostaglandin dehydrogenase (15-PGDH), the enzyme that inactivates PGs and (iii) decreasing the expression of EP and FP PG receptors that are essential for PG signaling. Since PGs have been shown to promote carcinogenesis and progression of multiple cancers, we hypothesize that the inhibition of the PG pathway contributes to the ability of calcitriol to prevent or inhibit PCa development and growth. We have shown that the combination of calcitriol and non-steroidal anti-inflammatory drugs (NSAIDs) result in a synergistic inhibition of the growth of PCa cell cultures and this combination therapy offers a potential therapeutic strategy. These findings led us to embark on a clinical trial combining the non-selective NSAID naproxen with calcitriol in men with early recurrent PCa. The results indicate that the combination of high dose weekly calcitriol with naproxen slows the rate of rise (doubling time) of PSA in most patients indicating the slowing of disease progression. Further studies are warranted to determine the role of this combination therapy in the management of recurrent PCa.

    View details for PubMedID 20046582

  • The Combination of Thalidomide and Capecitabine in Metastatic Renal Cell Carcinoma - Is Not the Answer AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Harshman, L. C., Li, M., Srinivas, S. 2008; 31 (5): 417-423

    Abstract

    Despite the introduction of newer treatment approaches in metastatic renal cell carcinoma (mRCC), overall survival remains disappointing and further exploration of current chemotherapeutic agents for second or third-line treatment is imperative. We conducted a phase II trial to determine the efficacy and safety of the combination of thalidomide and capecitabine in mRCC.We enrolled 13 eligible patients, who had progressive measurable metastatic disease, between May 2003 and January 2005. Treatment consisted of thalidomide 200 mg daily for 21 days per cycle, and capecitabine 1250 mg/m(2) twice daily for 14 days per cycle. The primary end point was response rate. Secondary endpoints included overall survival and toxicity assessment.Twelve patients were eligible for statistical analysis. The median age was 59 years, and most patients had an Eastern Cooperative Oncology Group performance status of 0-1 (92%). Nine patients had previous nephrectomy. The median number of administered cycles was 4 (range 2-10). Anemia was the only grade 3 toxicity. Grade 2 toxicities included fatigue, constipation, anemia, hand-foot syndrome, diarrhea, and peripheral neuropathy. Although no radiographic responses were observed, 5 patients (42%) achieved stable disease. Seven patients (58%) experienced disease progression. The median overall survival was 10.2 months.Despite being well tolerated with manageable side effects, the use of thalidomide and capecitabine in patients with mRCC did not significantly impact response or survival.

    View details for DOI 10.1097/COC.0b013e318168ef47

    View details for Web of Science ID 000260123000003

    View details for PubMedID 18838876

  • Cardiotoxicity associated with the cancer therapeutic agent sunitinib malate ANNALS OF ONCOLOGY Telli, M. L., Witteles, R. M., Fisher, G. A., Srinivas, S. 2008; 19 (9): 1613-1618

    Abstract

    In the pivotal phase III metastatic renal cell carcinoma trial, updated data indicates that 21% of sunitinib-treated patients experienced a decline in left ventricular ejection fraction to below normal. This cardiotoxicity was reported to be reversible and without clinical sequelae. We conducted a retrospective analysis of our institutional experience of cardiotoxicity with sunitinib after observing a high incidence of symptomatic heart failure.Patients receiving sunitinib at Stanford University from 1 July 2004 to 1 July 2007 were identified. Medical records were reviewed and those patients experiencing symptomatic grade 3/4 left ventricular systolic dysfunction were identified. Potential cardiac risk factors were analyzed.Forty-eight patients treated with sunitinib were assessable. Seven patients experienced symptomatic grade 3/4 left ventricular dysfunction 22-435 days after initiation of sunitinib. Three patients had persistent cardiac dysfunction after discontinuation of sunitinib and initiation of heart failure therapy. A history of congestive heart failure, coronary artery disease and lower body mass index were factors associated with increased risk.Among patients treated with sunitinib at our institution, 15% developed symptomatic grade 3/4 heart failure. Future studies of sunitinib-related cardiotoxicity are urgently needed, particularly as the oncologic indications for this drug continue to expand.

    View details for DOI 10.1093/annonc/mdn168

    View details for Web of Science ID 000259505400015

    View details for PubMedID 18436521

  • Phase 2 trial of talactoferrin in previously treated patients with metastatic renal cell carcinoma CANCER Jonasch, E., Stadler, W. M., Bukowski, R. M., Hayes, T. G., Varadhachary, A., Malik, R., Figlin, R. A., Srinivas, S. 2008; 113 (1): 72-77

    Abstract

    Talactoferrin (TLF), a recombinant form of human lactoferrin (hLF), is an immunomodulatory iron-binding glycoprotein first identified in breast milk. Its immunomodulatory functions include activation of natural killer (NK) and lymphokine-activated killer cells and enhancement of polymorphonuclear cells and macrophage cytotoxicity. Studies in animal models have shown promising anticancer activity, and clinical antitumor activity has been observed in nonsmall cell lung cancer and other tumor types. The purpose of the current study was to evaluate the activity and safety of TLF in patients with refractory metastatic renal cell carcinoma (RCC).Forty-four adult patients with progressive advanced or metastatic RCC who had failed prior systemic therapy received oral talactoferrin at a dose of 1.5 g twice daily on a 12-week-on 2-week-off schedule. Patients were evaluated for progression-free survival at 14 weeks, overall response rate, and progression-free and overall survival.TLF was well tolerated. No significant hematologic, hepatic, or renal toxicities were reported. The study met its predefined target with a 14-week progression-free survival rate of 59%. The response rate was 4.5%. The mMedian progression-free survival was 6.4 months and the median overall survival was 21.1 months.TLF is a well-tolerated new agent that has demonstrated preliminary signs of clinical activity. Given the lack of toxicity, the lack of rapid disease progression in this cohort, and the preclinical data on immune activation, a randomized study assessing its effects on disease progression in patients with metastatic RCC is rational.

    View details for DOI 10.1002/cncr.23519

    View details for Web of Science ID 000256914200010

    View details for PubMedID 18484647

  • Continuous daily dosing of sunitinib in patients with metastatic renal cell cancer ONKOLOGIE Harshman, L., Srinivas, S. 2008; 31 (8-9): 432-433

    View details for DOI 10.1159/000144179

    View details for Web of Science ID 000259273700004

    View details for PubMedID 18787349

  • Current status of cytoreductive nephrectomy in metastatic renal cell carcinoma EXPERT REVIEW OF ANTICANCER THERAPY Harshman, L. C., Srinivas, S. 2007; 7 (12): 1749-1761

    Abstract

    The incidence of metastatic renal cell carcinoma (mRCC) continues to rise. While treatment options have increased dramatically in the last few years, few patients achieve a cure. The standard of care for mRCC in cytokine-eligible candidates is nephrectomy followed by high-dose IL-2. High-dose IL-2 can induce durable complete remissions, but only select patients can enjoy its benefits owing to toxicities. While not curative, the newer targeted therapies offer a broader patient population the chance for treatment response and prolonged survival. This review highlights the historical background of cytoreductive nephrectomy in mRCC, discusses the available treatment options and considers alternative treatment paradigms, such as the integration of the targeted agents with nephrectomy and the use of systemic therapy as medical selection for determining appropriate nephrectomy candidates.

    View details for DOI 10.1586/14737140.7-12.1749

    View details for Web of Science ID 000251891100016

    View details for PubMedID 18062749

  • Randomized phase II study of erlotinib combined with bevacizumab compared with bevacizumab alone in metastatic renal cell cancer JOURNAL OF CLINICAL ONCOLOGY Bukowski, R. M., Kabbinavar, F. F., Figlin, R. A., Flaherty, K., Srinivas, S., Vaishampayan, U., Drabkin, H. A., Dutcher, J., Ryba, S., Xia, Q., Scappaticci, F. A., McDermott, D. 2007; 25 (29): 4536-4541

    Abstract

    Bevacizumab (Bev) has clinical activity in advanced renal cell carcinoma (RCC), and, when combined with erlotinib (Erl), has shown encouraging objective response rate (ORR) and progression-free survival (PFS). We performed a phase II, randomized, double-blind, multicenter, placebo-controlled trial to assess whether Erl provides additional clinical benefit with regard to PFS and ORR when combined with Bev in first-line treatment of metastatic RCC.One hundred four patients received intravenous Bev (10 mg/kg) every 2 weeks in combination with oral Erl (150 mg) or placebo daily. Patients were treated until progression or toxicity.A landmark analysis was performed 9 months after enrollment was completed (median follow-up, 9.8 months). Sixty-five patients had discontinued therapy; time to study discontinuation did not differ between the two treatment groups. The median PFS was 9.9 months (Bev + Erl [B+E]) versus 8.5 months (Bev; hazard ratio = 0.86; 95% CI, 0.5 to 1.49; P = .58). ORR (complete plus partial) was 14% (B+E) versus 13% (Bev). One complete response occurred in the B+E group. Median survival was 20 months for B+E but not reached for Bev. The most common grade 3/4 adverse events (> 5% of patients) were hypertension, rash, proteinuria, diarrhea, and hemorrhage. One treatment-related death occurred on study (GI perforation, B+E group).The addition of Erl to Bev was well tolerated, but did not provide additional clinical benefit compared with Bev alone. Bev has encouraging clinical activity for previously untreated metastatic RCC patients.

    View details for DOI 10.1200/JCO.2007.11.5154

    View details for Web of Science ID 000251073600008

    View details for PubMedID 17876014

  • Acute pancreatitis associated with sorafenib SOUTHERN MEDICAL JOURNAL Li, M., Srinivas, S. 2007; 100 (9): 909-911

    Abstract

    Since its FDA approval in December 2005, sorafenib (Nexavar) has been in use for the treatment of metastatic renal cell carcinoma. With this increased use have come reports of adverse effects of sorafenib. To the best of the authors' knowledge, they are the first to describe an 80-year-old Asian male with a history of metastatic renal cell carcinoma who developed acute pancreatitis confirmed by computed tomography (CT) one month after taking sorafenib 400 mg orally twice a day. Sorafenib was eventually discontinued, and the pancreatitis resolved. The molecular biologic mechanism causing this side effect is discussed. Patients should be informed of this rare but potentially serious adverse effect before initiation of sorafenib therapy. Early recognition of this complication and complete discontinuation of sorafenib are recommended.

    View details for Web of Science ID 000249669600014

    View details for PubMedID 17902294

  • Prostate cancer. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network Mohler, J., Babaian, R. J., Bahnson, R. R., Boston, B., D'Amico, A., Eastham, J. A., Hauke, R. J., Huben, R. P., Kantoff, P., Kawachi, M., Kuettel, M., Lange, P. H., Logothetis, C., MacVicar, G., Pollack, A., Pow-Sang, J. M., Roach, M., Sandler, H., Shrieve, D., Srinivas, S., Twardowski, P., Urban, D. A., Walsh, P. C. 2007; 5 (7): 650-683

    View details for PubMedID 17692170

  • Vitamin D inhibition of the prostaglandin pathway as therapy for prostate cancer NUTRITION REVIEWS Feldman, D., Krishnan, A., Moreno, J., Swami, S., Peehl, D. M., Srinivas, S. 2007; 65 (8): S113-S115

    View details for Web of Science ID 000248995500012

    View details for PubMedID 17867384

  • Bone related events in high risk prostate cancer JOURNAL OF UROLOGY Srinivas, S., Colocci, N. 2006; 176 (6): S50-S54

    Abstract

    We provide recommendations for defining and treating bone related events in high risk prostate cancer.A focused literature review was done.Men with prostate cancer often have osteoporosis and osteopenia even before initiating androgen deprivation therapy. After starting androgen deprivation therapy they experience accelerated bone loss. Bone mineral density is the most common tool to assess the degree of bone loss, although the use of bone turnover markers for this purpose is being actively explored. Bisphosphonates are effective for increasing bone mineral density and treating osteoporosis. The benefits derived from bisphosphonates should be weighed against the adverse effects, including the risk of osteonecrosis of the jaw. Treatment is indicated in patients with prostate cancer with osteoporosis and it may be considered in patients with osteopenia and/or additional risk factors. The time of initiation of therapy and duration of treatment have not been conclusively established.Prolonged androgen deprivation therapy results in bone loss and it has a potential to impact quality of life. Additional research is needed to characterize patients who would benefit from therapy and optimize strategies to prevent osteoporosis.

    View details for DOI 10.1016/j.juro.2006.06.076

    View details for Web of Science ID 000242029200011

    View details for PubMedID 17084167

  • Reliability of small amounts of cancer in prostate biopsies to reveal pathologic grade UROLOGY King, C. R., McNeal, J. E., Gill, H., Brooks, J. D., Srinivas, S., Presti, J. C. 2006; 67 (6): 1229-1234

    Abstract

    To examine grade reliability when biopsies contain very small amounts of prostate cancer. Prostate biopsy findings are known to undergrade prostate cancer compared with the pathologic specimens yet remain the only grade guiding disease management.The presence of a clinically significant grade change from biopsy cores to matched prostatectomy specimens was examined in 371 patients. The biopsies were characterized for primary and secondary Gleason grade, number of positive cores, and total linear length of cancer. The pathologic specimens were characterized for cancer volume and relative percentage by grade. The rates of upgrading or downgrading were tested against all clinical and biopsy information for any significant predictive value.The overall rate of upgrading was 40.7% and downgrading was 16.1%. Upgrading was constant and independent of any clinical or biopsy tumor volume indexes. Specifically, when cancer was present in only one biopsy core and measured 2 mm or less (n = 48), it was just as predictive of the pathologic grade as that from any greater number of positive cores and any greater extent of cancer length present. Downgrading was less frequent for biopsies with small amounts of cancer.Histologic grading from small amounts of cancer in prostate biopsies is reliable and not more prone to grading errors. A repeat biopsy for these patients may not be indicated.

    View details for DOI 10.1016/j.urology.2005.12.031

    View details for Web of Science ID 000238390900026

    View details for PubMedID 16765184

  • Nonplatinum therapy in advanced bladder cancer EXPERT REVIEW OF ANTICANCER THERAPY Srinivas, S., Colocci, N. 2006; 6 (6): 887-894

    Abstract

    Carcinoma of the bladder is the second most prevalent genitourinary malignancy and the fifth most common solid malignancy in the USA. Combination chemotherapy is used in most patients with advanced disease. Traditionally, on the basis of favorable response rates and survival data, cisplatin-based regimens have been the preferred chemotherapy for patients with metastatic bladder cancer. However, the toxicity profile of cisplatin precludes its use in a significant subset of patients with advanced bladder cancer. Conversely, noncisplatin-containing regimens have been shown to have a more favorable toxicity profile and to have activity in advanced bladder cancer. Here, various nonplatinum chemotherapy regimens for advanced disease are reviewed.

    View details for DOI 10.1586/14737140.6.6.887

    View details for Web of Science ID 000240923100013

    View details for PubMedID 16761932

  • Phase II study evaluating oral triamcinolone in patients with androgen-independent prostate cancer UROLOGY Srinivas, S., Krishnan, A. V., Colocci, N., Feldman, D. 2006; 67 (5): 1001-1006

    Abstract

    To assess the effect of triamcinolone administration on the serum prostate-specific antigen (PSA) response and the time to progression in patients with androgen-independent prostate cancer (AIPC).Patients with AIPC were prospectively treated with oral triamcinolone 4 mg twice daily, and their serum PSA and cortisol levels were measured monthly. Patients with greater than 25% increases in serum PSA from baseline were considered to have progressive disease and were removed from the study. Those patients who had a decrease in serum PSA levels or stable disease continued in the study until disease progression. Bone scans were obtained every 12 weeks and at progression.Twenty-four patients with AIPC were treated from November 2002 to June 2004. A partial response with a more than 50% decrease in serum PSA level was seen in 29%. Another 21% achieved stable disease. No statistically significant difference was found in the time to progression in the partial responders and patients with stable disease. The median time to progression in both groups was 7.5 months. Treatment was well tolerated without any grade 3 or 4 toxicity.Oral triamcinolone was well tolerated by patients with AIPC, with 50% of the patients exhibiting a good response to therapy in terms of serum PSA level and time to progression.

    View details for DOI 10.1016/j.urology.2005.11.004

    View details for Web of Science ID 000238390800026

    View details for PubMedID 16698360

  • Evaluation of fluorodeoxyglucose positron emission tomography imaging in metastatic transitional cell carcinoma with and without prior chemotherapy UROLOGIA INTERNATIONALIS Liu, I. J., Lai, Y., Espiritu, J. I., Segall, G. M., Srinivas, S., Nino-Murcia, M., Terris, M. K. 2006; 77 (1): 69-75

    Abstract

    This study was designed to determine the value of fluorodeoxyglucose (FDG) positron emission tomography (PET) in the evaluation of metastatic transitional cell carcinoma (TCC).Fifty-eight FDG PET scans were performed on 46 consecutive patients with TCC. Results were correlated with radiologic, pathologic, and histologic findings in these patients and the sensitivity of PET for detecting malignancy in untreated TCC patients (n = 48) was compared to the sensitivity in patients who had undergone prior chemotherapy (n = 10).Of 48 scans in patients who had no prior systemic chemotherapy, 10 had increased uptake in proven metastatic TCC lesions and 3 PET studies failed to reveal metastatic TCC (sensitivity 76.9%). In patients free of metastatic disease, 33 revealed no abnormal uptake and 1 study revealed a suspicious area in a patient free of metastases (specificity = 97.1%). However, in 10 patients imaged after receiving chemotherapy, the sensitivity fell to 50% for the detection of histologically confirmed residual/recurrent tumor by PET.FDG PET detects increased metabolic activity. After chemotherapy, viable cancer cells may still be present but with a diminished metabolic rate. As a result, PET imaging is often useful in the evaluation of untreated metastatic TCC metastasis but should be interpreted with caution in patients who have received prior chemotherapy.

    View details for DOI 10.1159/000092937

    View details for Web of Science ID 000238913100014

    View details for PubMedID 16825819

  • Case 3. Photo therapy recall with gemcitabine following ultraviolet B treatment JOURNAL OF CLINICAL ONCOLOGY Badger, J., Uzieblo, A., Srinivas, S., Kang, S. W. 2005; 23 (28): 7224-7225
  • A lower dose of thalidomide is better than a high dose in metastatic renal cell carcinoma BJU INTERNATIONAL Srinivas, S., Guardino, A. E. 2005; 96 (4): 536-539

    Abstract

    To conduct a dose-finding trial using a single low dose and dose escalation of a higher dose of thalidomide in patients with metastatic renal cell carcinoma (RCC), and to evaluate the antineoplastic effectiveness of thalidomide as an anti-angiogenic agent on RCC.The 14 patients enrolled in the study had progressive measurable metastatic RCC and consented to participate. Patients were randomized to either a fixed low dose of 200 mg of thalidomide or to a high dose of 800 mg that was increased to a maximum dose of 1200 mg daily. Patients were evaluated for response after 8 weeks of therapy.Stable disease was achieved in six patients and was seen in both the low-dose and high-dose thalidomide groups. The median overall survival was 9 months. The low-dose thalidomide regimen was better tolerated and patients survived longer than those on the high-dose regimen (16 vs 6 months, P = 0.04)The use of low-dose thalidomide in patients with metastatic RCC was well tolerated and they survived for longer than those on the high-dose regimen.

    View details for DOI 10.1111/j.1464-410X.2005.05680.x

    View details for Web of Science ID 000231387900017

    View details for PubMedID 16104906

  • A nonplatinum combination in metastatic transitional cell carcinoma AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Srinivas, S., Guardino, A. E. 2005; 28 (2): 114-118

    Abstract

    Cisplatin-based chemotherapy is the most effective standard treatment available for patients with metastatic bladder cancer. For those patients who are unable to receive cisplatin, other effective combination treatments are needed. The objective of this research was to determine if a combination of paclitaxel and gemcitabine would be effective in patients who were unable to receive cisplatin or have failed cisplatin treatment.Patients with histologic-proven metastatic bladder cancer who had measurable disease were eligible. Patients received chemotherapy (in an outpatient clinic) with paclitaxel at 110 mg/m2 plus 1000 mg/m2 gemcitabine on days 1 and 15 of a 28-day cycle. Patients were evaluated after 2 cycles of therapy using computed tomography and bone scan imaging.An objective response rate was achieved in 61% of the patients (13 of 18 subjects). Fifty-five percent of the patients who were previously treated with chemotherapy had an objective response (11 of 18 subjects). The median duration of response was 5 months and the toxicity was mild. All patients with low-risk disease had a response (8 of 18 subjects), compared with a 30% response rate in the intermediate-/high-risk group (P = 0.001, 10 of 18 subjects).The combination of paclitaxel and gemcitabine given in an every 2-week regimen is very well tolerated and has significant activity in previously treated patients with metastatic transitional cell carcinoma. The combination of paclitaxel and gemcitabine appears to be effective for patients with good-risk disease who are unable to take cisplatin-based chemotherapy.

    View details for DOI 10.1097/01.coc.0000143018.04650.f9

    View details for Web of Science ID 000228240600002

    View details for PubMedID 15803002

  • Node Positive Bladder Cancer Arab J Urology Srinivas S, Freiha F 2005; 3: 7-11
  • Synchronous solitary metastasis of transitional cell carcinoma of the bladder to the testis UROLOGY Morgan, K., Srinivas, S., Freiha, F. S. 2004; 64 (4)

    Abstract

    Primary tumors known to metastasize to the testis, in order of decreasing frequency, are prostate, lung, gastrointestinal tract, melanoma, and kidney tumors. Metastasis from bladder cancer to the testis is extremely rare, occurs with advanced and metastatic disease, and is usually a finding at autopsy. We report a rare, and probably the first, case of solitary and synchronous metastatic transitional cell carcinoma of the bladder to the testis, discovered on the preoperative workup. An incidentally discovered testicular mass in a man with high-grade, invasive bladder cancer should be considered a metastatic lesion until proven otherwise.

    View details for Web of Science ID 000224680300054

    View details for PubMedID 15491734

  • Flutamide administration at 500 mg daily has similar effects on serum testosterone to 750 mg daily JOURNAL OF ANDROLOGY Murphy, J. C., Srinivas, S., Terris, M. K. 2004; 25 (4): 630-634

    Abstract

    A prior comparison of 750 mg flutamide daily to 500 mg daily with an LHRH analog or orchiectomy showed no difference in effect on prostate specific antigen (PSA). However, any difference was likely masked by hypogonadism from concomitant LHRH analog or orchiectomy. We sought to evaluate different flutamide dosing schedules without this confounding factor. We recruited 50 men with advanced prostate cancer who elected to receive hormonal therapy to be randomized to 1 of 3 flutamide treatment groups: 1) 250 mg once daily, 2) 250 mg twice daily, or 3) 250 mg 3 times daily for 3 months, after which the therapy of their choice was instituted. Serum samples at the initiation of therapy and at the 1- and 3-month time point were assessed for PSA, testosterone, liver function tests, hematology, and renal function. Prostate volume, androgen deficiency symptoms, and a compliance diary were also recorded. Testosterone and PSA levels show a dose-dependent response to flutamide monotherapy. Loss of libido and erectile dysfunction occurred in all 3 treatment groups, with a trend toward worsening sexual function with higher flutamide dosing, but this trend did not reach statistical significance. Prostate volumes decreased by an average of 34.3% in the patients receiving 250 mg flutamide 3 times daily, 27.8% in patients receiving 250 mg flutamide twice daily, and 19.2% in those receiving a once daily dose of 250 mg flutamide. There was a significant difference between the once daily group and the 3 times daily group (P =.047). Flutamide at 500 mg did not result in significant changes in testosterone, PSA, prostate volume, or androgen deficiency symptoms compared to 750 mg daily after 3 months.

    View details for Web of Science ID 000222455000022

    View details for PubMedID 15223852

  • Positron emission tomography in the initial staging of esophageal cancer ARCHIVES OF SURGERY Wren, S. M., Stijns, P., Srinivas, S. 2002; 137 (9): 1001-1006

    Abstract

    To assess the value of positron emission tomography (PET) compared with computed tomography (CT) in the initial staging of esophageal cancer.Case series.Tertiary care veterans hospital.Patients with newly diagnosed esophageal cancers from January 1996 through May 2001 who underwent both CT and PET scanning within 4 weeks were included in the study (n = 24). Only patients who underwent pathological or radiographic follow-up were included.The sensitivity, specificity, and negative and positive predictive values of CT and PET were determined based on a criterion standard of pathological staging in 16 patients (67%) and follow-up imaging in 8 patients (33%).For staging regional lymph node involvement, CT and PET scans showed no statistically significant difference in sensitivity (57% and 71%, respectively) and specificity (71% and 86%, respectively). For detection of metastatic disease, CT and PET showed no significant difference in sensitivity (83% and 67%, respectively) and specificity (75% and 92%, respectively). There was no significant difference in clinical decision making when the results of both tests were discordant.There was no significant difference between the 2 imaging modalities in the initial staging of esophageal cancer. The CT scan was a sensitive indicator of distant metastases, whereas PET was more specific. It is unclear what additional role PET scanning should have in the initial screening of patients.

    View details for Web of Science ID 000177920800004

    View details for PubMedID 12215149

  • Utility of bone scan post primary therapy in prostate cancer UroOncology Srinivas S 2002; 2: 37-39
  • Management choices in stage I non-seminomatous Germ Cell Tumor UroOncology Srinivas S, Terris MK 2001; 1: 1-4
  • High-dose chemotherapy in poor-risk germ-cell tumors ONCOLOGY-NEW YORK Srinivas, S. 2000; 14 (10): 1419-1423

    Abstract

    Testicular cancer is a highly curable cancer. However, 30% of patients are refractory to standard therapy and will need additional therapy. This article focuses on the use of high-dose chemotherapy in germ-cell tumors. High-dose chemotherapy use is discussed both in the refractory setting and as either first-salvage or first-line therapy. Various criteria for risk assessment are also discussed.

    View details for Web of Science ID 000090129800010

    View details for PubMedID 11098508

  • Spontaneous pneumothorax in malignancy: A case report and review of the literature ANNALS OF ONCOLOGY Srinivas, S., Varadhachary, G. 2000; 11 (7): 887-889

    Abstract

    Pneumothorax occurring in the absence of obvious lung disease is defined as spontaneous pneumothorax. Spontaneous pneumothorax occurs in a variety of settings in patients with malignancies.We present a case report of spontaneous pneumothorax in malignancy and review the literature.No correlation was found between the occurrence of pneumothorax with age, sex or smoking history. Pneumothorax occurred with a variety of primary tumors. However it was always associated with lung metastases or lung involvement with tumor. In certain cases the metastases were detected after the occurrence of pneumothorax.The occurrence of pneumothorax in a patient with malignancy should prompt a search for lung metastases.

    View details for Web of Science ID 000089244400026

    View details for PubMedID 10997821

  • Comparison of FDG-PET and Bone Scans for Detecting Skeletal Metastases in Patients with Non-small Cell Lung Cancer. Clinical positron imaging : official journal of the Institute for Clinical P.E.T Durski, J. M., Srinivas, S., Segall, G. 2000; 3 (3): 97-105

    Abstract

    Purpose: Positron Emission Tomography (PET) with F18-fluorodeoxyglucose has been proven useful for staging non-small cell lung cancer. Bone scans are frequently performed for suspected skeletal metastases. The purpose of this study was to evaluate if bone scans compared to PET scans provide additional information that changes the stage of disease.Procedures: Nineteen patients with non-small cell lung cancer had PET and bone scans done for staging of the malignancy. The results of both studies were compared.Results: Bone and PET scans agreed on the presence or absence of skeletal metastases in all nineteen patients. The addition of a bone scan to a PET scan did not change the stage of the disease or the management in any of the patients. Bone scans allowed for more precise localization of the lesions in some patients.Conclusions: Bone scans do not change the stage of disease when performed in addition to PET scans, but provide more precise localization of skeletal abnormalities.

    View details for PubMedID 11008099

  • Actinomycin D revisited in testicular cancer. A case report TUMORI Srinivas, S., Freiha, F. S. 1999; 85 (1): 78-79

    Abstract

    Between 20-30% of patients with advanced germ cell tumors relapse or fail to achieve a complete response to conventional cisplatin based chemotherapy. Ifosphamide has been used very effectively in combination with cisplatin and etoposide (VIP) or in combination with cisplatin and vinblastine (VeIP). Actinomycin D with chlorambucil and methotrexate was widely used in the 1960s with complete responses in 20% of patients and long term survival of 6-10%. There exists no information on the use of actinomycin as a salvage in cisplatin refractory patients.One patient with metastatic germ cell tumor who failed chemotherapy with cisplatin and ifosphamide was successfully treated with an actinomycin D based regimen.Actinomycin D is an active agent in testicular cancer and maybe used in patients refractory to platinum.

    View details for Web of Science ID 000080742700018

    View details for PubMedID 10228505

  • Methotrexate tolerance in patients with ileal conduits and continent diversions CANCER Srinivas, S., Mahalati, K., Freiha, F. S. 1998; 82 (6): 1134-1136

    Abstract

    Methotrexate is readily absorbed from the intestinal tract. When given to patients with urinary diversion to the intestinal tract, methotrexate may be reabsorbed into the circulation, thus increasing its serum concentration and potentially increasing its toxicity.Forty-eight patients with transitional cell carcinoma of the urinary tract who had undergone cystectomy and either an ileal conduit or a continent diversion were evaluated for their tolerance of chemotherapy. Of the 42 evaluable patients, 23 had a continent diversion and 19 had an ileal conduit. None of the patients with the continent diversion had an indwelling Foley catheter during the course of chemotherapy.There were no statistically significant differences in incidence of fever or neutropenia, mucositis, dose modification, or delay in chemotherapy between the two groups. When compared with a group of patients with native bladders who received the same chemotherapy, patients with continent diversions did not have increased incidence or severe toxicity from chemotherapy.Patients with continent diversions tolerated chemotherapy as well as patients with ileal conduits.

    View details for Web of Science ID 000072376400018

    View details for PubMedID 9506360

  • Doxorubicin and dose-escalated cyclophosphamide with granulocyte colony-stimulating factor for the treatment of hormone-resistant prostate cancer JOURNAL OF CLINICAL ONCOLOGY Small, E. J., Srinivas, S., Egan, B., McMillan, A., Rearden, T. P. 1996; 14 (5): 1617-1625

    Abstract

    The goals of this study were to define the efficacy and toxicity of doxorubicin and dose-escalated cyclophosphamide (Cy) along with granulocyte colony-stimulating factor (G-CSF) in the treatment of hormone-refractory prostate cancer (HRPC), to determine the maximal-tolerated dose (MTD) of Cy in this regimen, and to evaluate the impact of prior pelvic irradiation (XRT) on MTD and toxicity.Thirty-five patients were treated every 21 days with fixed-dose doxorubicin (40 mg/m2) and Cy 800 to 2,000 mg/m2 (in a cohort dose-escalation schema) along with G-CSF.Five of 15 patients (33%) with measurable disease obtained an objective response. Sixteen of 35 patients (46%) had a greater than 50% decrease in prostate-specific antigen (PSA) level (95% confidence interval [CI], 28.8% to 63.4%). Ten of 35 patients (28.6%) had a greater than 75% decrease in PSA level. The median survival time was 11 months. The median survival duration of patients with a greater than 50% decrease in PSA level was 23 months, versus a median survival time of 7 months in patients without a PSA response (P = .02). Although 33% of cycles were associated with grade 4 neutropenia, febrile neutropenia occurred in only 7.8% of all cycles. Thrombocytopenia and anemia were rare. Nonhematologic toxicity was minimal. Patients who had received prior pelvic XRT had a lower Cy MTD, but their hematologic toxicity was not appreciably different.This is a well-tolerated, active regimen for the treatment of HRPC. Toxicity was not different in patients with prior pelvic XRT, although these patients had a lower MTD.

    View details for Web of Science ID A1996UJ40300029

    View details for PubMedID 8622080

  • THE ANTIANDROGEN WITHDRAWAL SYNDROME - EXPERIENCE IN A LARGE COHORT OF UNSELECTED PATIENTS WITH ADVANCED PROSTRATE CANCER CANCER Small, E. J., Srinivas, S. 1995; 76 (8): 1428-1434

    Abstract

    Flutamide withdrawal has been reported to be therapeutically efficacious for patients with hormone-refractory prostate cancer, with a reported prostate specific antigen (PSA) response rate of 29%.to evaluate the results of flutamide withdrawal in a large group of unselected patients, the medical records of 107 consecutive patients with metastatic prostate cancer who developed progressive disease while receiving flutamide therapy were reviewed retrospectively. Flutamide withdrawal was undertaken at the time of disease progression.Eighty-two patients were evaluable. Of these, three had a > 80% fall in PSA value, and another nine had a > 50% decrease, for a response proportion of 14.6% (95% confidence interval 7.8%-24.2%). The median response duration was 3.5 months (range, 1-12+ months). Eight of patients treated with combined androgen blockade at the time of diagnosis of metastatic disease had a response (14%), whereas 4/25 responses (16%) were noted in patients in whom flutamide was added later, at the time of first progression. When patients who responded were compared with patients who did not respond, there was not a significant difference in age, pretreatment PSA level, type of gonadal androgen deprivation, or the likelihood of prior combined androgen blockade versus late addition of flutamide. The duration of prior therapy with flutamide was longer in patients who responded (21.5 vs. 12.0 months).These findings confirm the flutamide withdrawal phenomenon in a large group of unselected patients, although its frequency is not as high as previously reported. In contrast to earlier reports, whether patients have had initial hormonal therapy with combined androgen blockade or monotherapy does not appear to be predictive of the likelihood of response to antiandrogen withdrawal.

    View details for Web of Science ID A1995RY50600019

    View details for PubMedID 8620419

  • THE WEIGHT-BASED HEPARIN DOSING NOMOGRAM COMPARED WITH A STANDARD CARE NOMOGRAM - A RANDOMIZED CONTROLLED TRIAL ANNALS OF INTERNAL MEDICINE Raschke, R. A., Reilly, B. M., Guidry, J. R., Fontana, J. R., Srinivas, S. 1993; 119 (9): 874-881

    Abstract

    To determine whether an intravenous heparin dosing nomogram based on body weight achieves therapeutic anticoagulation more rapidly than a "standard care" nomogram.Randomized controlled trial.Two community teaching hospitals in Phoenix, Arizona, and Rochester, New York.One hundred fifteen patients requiring intravenous heparin treatment for venous or arterial thromboembolism or for unstable angina.Patients were randomized to the weight-based nomogram (starting dose, 80 units/kg body weight bolus, 18 units/kg per hour infusion) or the standard care nomogram (starting dose, 5000-unit bolus, 1000 units per hour infusion). Activated partial thromboplastin time (APTT) values were monitored every 6 hours, and heparin dose adjustments were determined by the nomograms.Activated partial thromboplastin times were measured using a widely generalizable laboratory method. The primary outcomes were the time to exceed the therapeutic threshold (APTT > 1.5 times the control) and the time to achieve therapeutic range (APTT, 1.5 to 2.3 times the control). Bleeding complications and recurrent thromboembolism were also compared.Kaplan-Meier curves for the primary outcomes favored the weight-based nomogram (P < 0.001 for both). In the weight-based heparin group, 60 of 62 patients (97%) exceeded the therapeutic threshold within 24 hours, compared with 37 of 48 (77%) in the standard care group (P < 0.002). Only one major bleeding complication occurred (in a standard care patient). Recurrent thromboembolism was more frequent in the standard care group; relative risk, 5.0 (95% CI, 1.1 to 21.9).The weight-based heparin nomogram is widely generalizable and has proved to be effective, safe, and superior to one based on standard practice.

    View details for Web of Science ID A1993MD71100002

    View details for PubMedID 8214998

  • INTRAVENOUS HEPARIN DOSING - PATTERNS AND VARIATIONS IN INTERNISTS PRACTICES JOURNAL OF GENERAL INTERNAL MEDICINE Reilly, B. M., Raschke, R., Srinivas, S., Nieman, T. 1993; 8 (10): 536-542

    Abstract

    To characterize internists' dosing practices when administering and adjusting intravenous heparin regimens.A survey administered by physician-investigators.Two community teaching hospitals and one Veterans Affairs Medical Center.Sixty-one attending physicians in internal medicine.Physicians' choices of therapeutic activated partial thromboplastin time (APTT) range, initial heparin bolus, initial infusion dose, and dose/infusion adjustments when APTT levels are < 1.2 x control (< 35 seconds), 1.2-1.5 x control (35-45 seconds), 1.5-2.3 x control (46-70 seconds), 2.3-3.0 x control (71-90 seconds), and > 3.0 x control (> 90 seconds).Physicians' dosing decisions and therapeutic ranges during heparin treatment varied widely. Responses to nontherapeutic APTT levels had especially high coefficients of variation (0.67-0.81). Two groups of physicians, together comprising a majority of all respondents, use mutually exclusive therapeutic ranges (mean 44-56 seconds and 60-83 seconds). These two groups differ significantly in several types of dosing decisions.In the absence of generalizable standard guidelines for intravenous heparin therapy, internists' dosing practices vary widely. Because such practices may impede timely, effective anticoagulation, experimental studies comparing standardized dosing protocols are needed.

    View details for Web of Science ID A1993MC43800003

    View details for PubMedID 8271085

Conference Proceedings


  • Progressive decrease in bone density over 10 years of androgen deprivation therapy in patients with prostate cancer Kiratli, B. J., Srinivas, S., Perkash, I., Terris, M. K. ELSEVIER SCIENCE INC. 2001: 127-132

    Abstract

    Several reports suggest an increased incidence of osteoporosis and concomitant fractures in men receiving androgen deprivation therapy (ADT) for prostate cancer. We sought to estimate the longitudinal effects of ADT on loss of bone density in this cross-sectional study.Hip and spine bone mineral density (BMD) studies were performed by dual-energy x-ray absorptiometry on 36 patients with prostate cancer. The year 0 cohort (n = 8) consisted of patients who had not yet begun planned ADT. These men were compared to patients receiving ADT who underwent BMD evaluation at year 2 (n = 6), year 4 (n = 7), year 6 (n = 5), year 8 (n = 5), and year 10 (n = 5) of therapy. All BMD values for the patients with prostate cancer were compared to age-matched control subjects.Hip BMD was significantly lower in patients on ADT (mean BMD 0.802 g/cm(2)) compared with those not on ADT (mean BMD 0.935 g/cm(2)). Patients at year 0 had hip and spine BMD similar to age-matched control subjects. There was a significant trend for decreased hip BMD with increasing years of ADT (r = 0.46, P = 0.00008). This relationship was more dramatic when hip BMD at each time point was compared to age-matched control subjects (r = 0.55, P = 0.5 x 10(-16)). This bone loss was evident even up to year 10. BMD loss was more dramatic in patients who had undergone surgical castration than those receiving medical ADT (P = 0.08). Patients on intermittent ADT had similar BMD loss as patients on continuous ADT at year 2 and year 4 but demonstrated less bone loss at year 6 (P = 0.07) despite equivalently low testosterone levels.There is diminished BMD with increasing duration of ADT. Continuous ADT and surgical castration may be more deleterious than medical therapy, particularly when the medical therapy is given in an intermittent fashion.

    View details for Web of Science ID 000166663000025

    View details for PubMedID 11164157

  • Tool support for authoring eligibility criteria for cancer trials Rubin, D. L., Gennari, J. H., Srinivas, S., Yuen, A., Kaizer, H., Musen, M. A., Silva, J. S. BMJ PUBLISHING GROUP. 1999: 369-373

    Abstract

    A critical component of authoring new clinical trial protocols is assembling a set of eligibility criteria for patient enrollment. We found that clinical protocols in three different cancer domains can be categorized according to a set of clinical states that describe various clinical scenarios for that domain. Classifying protocols in this manner revealed similarities among the eligibility criteria and permitted some standardization of criteria based on clinical state. We have developed an eligibility criteria authoring tool which uses a standard set of eligibility criteria and a diagram of the clinical states to present the relevant eligibility criteria to the protocol author. We demonstrate our ideas with phase-3 protocols from breast cancer, prostate cancer, and non-small cell lung cancer. Based on measurements of redundancy and percentage coverage of criteria included in our tool, we conclude that our model reduces redundancy in the number of criteria needed to author multiple protocols, and it allows some eligibility criteria to be authored automatically based on the clinical state of interest for a protocol.

    View details for Web of Science ID 000170207300077

    View details for PubMedID 10566383

Stanford Medicine Resources: