A randomized, phase II study of pazopanib in castrate-sensitive prostate cancer: a University of Chicago Phase II Consortium/Department of Defense Prostate Cancer Clinical Trials Consortium study

J E Ward, T Karrison, G Chatta, M Hussain, D Shevrin, R Z Szmulewitz, P H O'Donnell, W M Stadler, E M Posadas, J E Ward, T Karrison, G Chatta, M Hussain, D Shevrin, R Z Szmulewitz, P H O'Donnell, W M Stadler, E M Posadas

Abstract

Background: Intermittent androgen suppression (IAS) is an increasingly popular treatment option for castrate-sensitive prostate cancer. On the basis of previous data with anti-angiogenic strategies, we hypothesized that pan-inhibition of the vascular endothelial growth factor receptor using pazopanib during the IAS off period would result in prolonged time to PSA failure.

Methods: Men with biochemically recurrent prostate cancer, whose PSA was <0.5 ng ml(-1) after 6 months of androgen deprivation therapy were randomized to pazopanib 800 mg daily or observation. The planned primary outcome was time to PSA progression >4.0 ng ml(-1).

Results: Thirty-seven patients were randomized. Of 18 patients randomized to pazopanib, at the time of study closure, 4 had progressive disease, 1 remained on treatment and 13 (72%) electively disenrolled, the most common reason being patient request due to grade 1/2 toxicity (8 patients). Two additional patients were removed from treatment due to adverse events. Of 19 patients randomized to observation, at the time of study closure, 4 had progressive disease, 7 remained under protocol-defined observation and 8 (42%) had disenrolled, most commonly due to non-compliance with protocol visits (3 patients). Because of high dropout rates in both arms, the study was halted.

Conclusions: IAS is a treatment approach that may facilitate investigation of novel agents in the hormone-sensitive state. This trial attempted to investigate the role of antiangiogenic therapy in this setting, but encountered several barriers, including toxicities and patient non-compliance, which can make implementation of such a study difficult. Future investigative efforts in this arena should carefully consider drug toxicity and employ a design that maximizes patient convenience to reduce the dropout rate.

Conflict of interest statement

CONFLICT OF INTEREST:

Dr. Posadas has received compensation from GlaxoSmithKline as a member of their speaker’s bureau. Drs. Ward, Karrison, Chatta, Hussain, Shevrin, Szmulewitz, O’Donnell and Stadler have nothing to disclose.

Figures

Figure 1
Figure 1
Schema for the randomized, placebo controlled, phase II study.
Figure 2
Figure 2
A: Flowchart of patient accrual and reasons for study discontinuation B: Patient outcomes including most common reasons for study discontinuation
Figure 2
Figure 2
A: Flowchart of patient accrual and reasons for study discontinuation B: Patient outcomes including most common reasons for study discontinuation

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