Docetaxel and capecitabine in metastatic androgen independent prostate cancer (AIPC): Phase II trial to detect clinical efficacy of a synergistic combination

Abstract

4703 Background: Docetaxel plus prednisone is the current therapeutic choice in the management of metastatic AIPC. Capecitabine is an oral prodrug of 5-fluorouracil which is selectively converted intratumorally to 5-flourouracil by thymidine phosphorylase (TP). Differential overexpression of TP is noted in tumors as compared to normal tissue. Docetaxel pretreatment when followed by capecitabine therapy has demonstrated synergy in preclinical studies with xenograft models. The purpose of this phase II trial was to evaluate the efficacy and safety of this combination in metastatic AIPC. Methods: Eligible patients had metastatic AIPC with no prior chemotherapy for metastatic disease. Other requirements included castrate levels of testosterone adequate renal, liver and marrow function and evidence of disease progression either by PSA, new metastatic sites, or progression of measurable disease sites. Docetaxel was administered intravenously on days 1, 8 and 15 of a 28 day cycle at a dose of 36 mg/m2. Capecitabine was administered at a dose of 1250 mg/m2/day in two divided doses orally from days 5 to 18 of each cycle. Results: 11 of 15 patients planned in the first stage have been enrolled to date. Baseline characteristics were, median age 73 years (range 38–78 years).;baseline PSA 131ng/ml (Range 8.9–3716ng/ml); three patients had progressive measurable disease, 5 patients had progression of bony metastases and 3 patients had PSA progression alone. 7 of the 8 evaluable patients demonstrated >50% decline in PSA and both of the measurable disease patients evaluated had a partial remission. 41 cycles of therapy (median 5 cycles) have been administered. Three patients required dose reduction. No grade 4/5 toxicities were noted. Only 1 patient had grade 3 neutropenia. No therapy related hospitalizations or deaths were observed. Conclusions: Preliminary data suggest that the combination of capecitabine and docetaxel is well tolerated and demonstrates promising activity in metastatic AIPC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Roche Aventis