Eligibility and Response Guidelines for Phase II Clinical Trials in Androgen-Independent Prostate Cancer: Recommendations From the Prostate-Specific Antigen Working Group

Bubley, Glenn J.; Carducci, Michael A.; Dahut, William L.; Dawson, Nancy A.; Daliani, Danai; Eisenberger, Mario A.; Figg, William D.; Freidlin, Boris; Halabi, Susan; Hudes, Gary R.; Hussain, Maha; Kaplan, Richard; Myers, Charles E.; Oh, William; Petrylak, Daniel P.; Reed, Eddie; Roth, Bruce J.; Sartor, Oliver; Scher, Howard I.; Simons, Jonathan W.; Sinibaldi, Victoria J.; Small, Eric J.; Smith, Matthew R.; Trump, Donald L.; Vollmer, Robin T.; Wilding, George

doi:10.1200/jco.1999.17.11.3461

Cited by 911 publications

(575 citation statements)

References 23 publications

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“…A PSA decrease of 50% or more from the baseline has been reported to be a surrogate biologic endpoint for response. 8,20 In our study, 11 patients (46%) had a significant PSA decline lasting at least 2 months and two patients obtained a stabilisation of PSA values (8%). The median duration of the response on PSA was 11.4 months.…”

Section: Discussionsupporting

confidence: 47%

“…Stable disease was defined by a decrease in PSA o50%. 8,18 Pain evaluation. A partial response in pain intensity was defined by a 425% improvement (ie decrease) from the baseline Visual Analog Scale measurement.…”

Section: Definition Of Responsementioning

confidence: 99%

“…5,6 Therefore, surrogate end points have been developed in the 1990s, such as changes in the prostate-specific antigen (PSA) serum levels and palliation. 7,8 In fact, some patients benefit from chemotherapy, as manifested by decreased pain or improved functional status. In view of the goal of treating HRPC (palliation), it is appropriate to consider alternative end points that might substantiate the clinical benefit of chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Mitoxantrone, vinorelbine and prednisone (MVD) in the treatment of metastatic hormonoresistant prostate cancer — a phase II trial

Bernardi

Talamini

Zanetti

et al. 2004

Prostate Cancer Prostatic Dis

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A total of 28 patients were treated with mitoxantrone, vinorelbine and prednisone every 3 weeks. In all, 11 patients (46%) had a significant prostate-specific antigen decline for a median duration of 11.4 months. Eight patients (33%) achieved a partial response on pain, while seven (29%) obtained a stabilisation of the symptom. Median duration of the response was 9.5 months. A confirmed partial response was obtained in three out of seven patients who had bidimensionally measurable disease. Toxicity was manageable. Our study provides further support to the concept of combined antimicrotubule therapy for metastatic harmonoresistant prostate cancer, promoting the exploration of new regimens containing antimicrotubule agents in addition to mitoxantrone-prednisone.

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Section: Discussionsupporting

confidence: 47%

Section: Definition Of Responsementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mitoxantrone, vinorelbine and prednisone (MVD) in the treatment of metastatic hormonoresistant prostate cancer — a phase II trial

Bernardi

Talamini

Zanetti

et al. 2004

Prostate Cancer Prostatic Dis

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“…1 To confirm surrogacy, one must therefore show a strong correlation between the treatment's relative effect on the surrogate and on the true end point in patients treated with a new versus standard intervention. 2 The PSA Working Group (PCWG1) 3 published criteria for a PSA partial response, which were strongly prognostic in studies of cytotoxic agents. However, despite extensive investigation, PSA has not been established as a surrogate end point in CRPC.…”

Section: Appraisal Of End Points In Phase II and Iii Trials In Castramentioning

confidence: 99%

Measuring therapeutic efficacy in the changing paradigm of castrate-resistant prostate cancer

Mulders

Schalken

2009

Prostate Cancer Prostatic Dis

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One of the current challenges in the evaluation of novel agents for the treatment of advanced prostate cancer is the identification of a surrogate end point for overall survival (OS). Prostatespecific antigen (PSA) levels have been used as a screening tool and a biomarker of response to both hormonal and cytotoxic agents. However, PSA levels do not seem to be a suitable surrogate end point for OS in trials of targeted agents for castrate-resistant prostate cancer (CRPC). These findings suggest the need for adopting measures of efficacy that more accurately reflect the mechanisms of action of these agents in phase II trials, in order to realize improvements in OS in the phase III setting. The Prostate Cancer Clinical Trials Working Group (PCWG2) have recently made recommendations for the design of future trials and advised that PSA levels should not be the sole criterion on which to base clinical decisions. Here, we appraise the end points that have been used in phase II and III trials in patients with CRPC, and highlight the need for the adoption of the PCWG2 guidelines, the recommendations of which include radiographic imaging, in addition to bone scintigraphy, and symptomatic or radiographic disease progression criteria.

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“…PSA responses were evaluated using the guidelines from the prostate-specific antigen working group for PSA response in androgen independent disease (Bubley et al, 1999). In the first cycle if the PSA was rising but there were clinical signs of improvement then a second cycle was given.…”

Section: Treatment and Evaluationmentioning

confidence: 99%

Chlorambucil and lomustine (CL56) in absolute hormone refractory prostate cancer: re-induction of endocrine sensitivity an unexpected finding

et al. 2004

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The management of androgen independent prostate cancer is increasingly disputed. Diethylstilbestrol and steroids have useful second-line activity in its management. The value of chemotherapy still remains contentious. This paper reports a phase 2 study of two orally active chemotherapy drugs in patients who are absolutely hormone refractory having failed primary androgen blockade and combined oestrogens and corticosteroids. In total, 37 patients who were biochemically castrate with absolute hormone refractory prostate cancer and performance status of 0 -3 were enrolled. Therapy consisted of chlorambucil 1 mg kg À1 given as 6 mg a day until the total dose was reached and lomustine 2 mg kg À1 given every 56 days (CL56). During this time all hormone therapy was stopped. One patient normalised his PSA with a further two having a greater than 50% decline leading to an objective response rate of 10%. The median time to progression was 3.6 months with an overall survival of 7.1 months. The median survival of this group of patients from first becoming androgen independent was 23.5 months. Eight of 17 (47%) patients who were subsequently rechallenged with hormonal therapy following failure of chemotherapy had a further PSA reduction, three (17%) of which were 450%. The median progression-free interval for the eight patients was 4 months. In conclusion, CL56 has a low objective response rate in the management of absolute hormone refractory prostate cancer. Toxicity was mild. Re-induction of hormone sensitivity following failure of chemotherapy was an unexpected finding that requires further study.

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Eligibility and Response Guidelines for Phase II Clinical Trials in Androgen-Independent Prostate Cancer: Recommendations From the Prostate-Specific Antigen Working Group

Abstract: Through this consensus conference, we believe we have developed practical guidelines for using PSA as a measurement of outcome. Furthermore, the use of common standards is important as we determine which agents should progress to randomized trials which will use survival as an end point.

Cited by 911 publications

References 23 publications

Mitoxantrone, vinorelbine and prednisone (MVD) in the treatment of metastatic hormonoresistant prostate cancer — a phase II trial

Mitoxantrone, vinorelbine and prednisone (MVD) in the treatment of metastatic hormonoresistant prostate cancer — a phase II trial

Measuring therapeutic efficacy in the changing paradigm of castrate-resistant prostate cancer

Chlorambucil and lomustine (CL56) in absolute hormone refractory prostate cancer: re-induction of endocrine sensitivity an unexpected finding

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