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ISRN Oncology  2012 

Pilot Phase II Trial of Bevacizumab Monotherapy in Nonmetastatic Castrate-Resistant Prostate Cancer

DOI: 10.5402/2012/242850

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Abstract:

Introduction/Background. Nonmetastatic castrate resistant prostate cancer (CRPC) is a challenging disease state. The objective of this study was to evaluate the efficacy and tolerability of bevacizumab in nonmetastatic CRPC patients. Patients. Patients with prostate cancer who developed PSA recurrence after local therapy were included if they had absence of bone or visceral metastases and PSA progression despite androgen deprivation therapy. Methods. Bevacizumab 10?mg/kg intravenously was administered every 14 days until PSA progression, development of metastasis, or unacceptable toxicity. Results. 15 patients were enrolled and treated with bevacizumab for a median duration of 3.1 months. Median baseline PSA was 27?ng/mL, and seven patients had Gleason Score ≥8. Five patients had declined in PSA during the treatment. Median PSA doubling time was prolonged from 4.7 months pretreatment to 6.5 months. Median time to PSA progression and new metastasis were 2.8 and 7.9 months, respectively. There were three grade 3 adverse events (one proteinuria and two hypertension) and one pulmonary embolism. There was no treatment-related mortality. Conclusion. Bevacizumab therapy had minimal impact on the disease course of nonmetastatic CRPC, and investigation of novel strategies is needed. 1. Background Approximately 30–40% of localized prostate-cancer patients develop biochemical relapse at 10 years after definitive local treatments [1–3]. Case series reports indicate that patients with prostate specific antigen (PSA) relapse will develop metastatic disease within a median duration of eight years, after biochemical failure [4]. Patients with high Gleason score (≥8), rapid PSA doubling time, and/or earlier PSA relapse after local treatment have higher risk of progression to metastatic disease during their lifespan and higher mortality [4, 5]. Currently no systemic therapy has proven efficacy in delaying the appearance of metastatic disease or improving survival after biochemical relapse (PSA failure). LHRH agonists are the most widely used agents in this setting. Although there is no solid evidence to support this strategy, randomized trials in metastatic disease certainly suggest that immediate use of androgen deprivation therapy (ADT) is associated with improved disease-specific mortality and morbidity, compared with delayed initiation of the therapy [6]. Unfortunately, progression on ADT eventually occurs, that is, nonmetastatic castrate-resistant prostate cancer (CRPC), and after that, this patient population is likely to continue progression to metastatic disease.

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