Oxaliplatin and docetaxel in castration-resistant prostate cancer (CRPC) patients treated with up to two prior chemotherapeutic regimens: Updated results of a phase II trial

Abstract

5148 Background: Docetaxel has a survival benefit in CRPC. Oral and IV platinum derivatives have activity in CRPC. We hypothesized that a novel combination of docetaxel and oxaliplatin may be beneficial in treating CRPC. Methods: A single arm phase II trial in patients with metastatic CRPC who were treated with docetaxel (60 mg/m2) and oxaliplatin (110 mg/m2) administered intravenously every 21 days for up to 6 cycles. The primary endpoint was response rate defined as a > 50% reduction in PSA levels, sustained for > 4 weeks. Secondary objectives were progression free survival (PFS), overall survival (OS), and toxicity (tolerance/safety). Results: 34 patients were accrued between June 2005 and August 2007. The median age was 66 years (49–84), with 24% over the age of 75. Prior therapies included androgen deprivation (100%); palliative radiation therapy (65%); and chemotherapy (44%), with 38% having received prior docetaxel. 68% of patients received all 6 cycles, with 80% of the maximum dose intensities of docetaxel and oxaliplatin being delivered. Median follow-up time was 15.75 months (range, 1.4–30.6 months). Median PSA at baseline was 370 ng/ml (range 1.5-3,559.4). 32 of the 34 patients were evaluable for response. Response rates are summarized in the table below. Four of 11 (36%) evaluable for response using RECIST had a partial response. Significant grade 3/4 hematologic adverse events (AE) were neutropenia (35%) and thrombocytopenia (6%). Grade 3/4 non-hematologic side effects were nausea (12%), dehydration (12%), diarrhea (9%), edema (6%), mucositis (6%) and infection (3%). Grade 2 or less neuropathy occurred in 71%. Conclusions: The combination of docetaxel and oxaliplatin has promising activity in CRPC. Toxicities were mostly hematologic and easily manageable. Randomized phase III trials with this novel regimen are warranted given the high PSA response rates, long progression free survival and overall survival. Prior chemotherapy Chemo-naïve Overall PSA decline >50% 9 of 14 (64%) (95% CI, 35%, 87%) 13 of 18 (72%) (95% CI, 46%, 90%) 22 of 32 (69%) (95% CI, 52%, 85%) PFS (median) 5.8 mo (95% CI, 3.5–6.4) 7.7 mo (95% CI, 4.9–10.4) 6.3 mo (95% CI, 4.9–7.7) OS (median) 14.9 mo (95% CI, 11.9–22.1) 24.7 mo (95% CI, 18–NA) 20.1 mo (95% CI, 15.1–NA) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis