1565P - Impact of a salvage chemotherapy with carboplatin plus docetaxel on testosterone levels in metastatic castration - and docetaxel-resistant prostate cancer (mDRPC)

Abstract

Recent data suggest that carboplatin plus docetaxel (DC) may be effective in mDRPC. Platinum(II)-complexes interfere with steroid biosynthesis by inhibiting the cholesterol side chain cleavage enzyme (CYP11A1), 3&bgr;-hydroxysteroid dehydrogenase (HSD3B1,2) and 17&agr; hydroxylase/C17,20-lyase (CYP17A1). Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Treatment consisted of at least two cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks, docetaxel at a dose of 35 mg/m2 iv for one hour on days 1, 8, 15 plus prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. Testosterone/androgene levels were measured before (n = 73) and during carboplatin/docetaxel chemotherapy (n = 63). Of the 96 pts. treated since February 2005, 95.8% had bone, 42.7% lymph node, 26.0% liver and 19.8% lung involvement. At the current analysis, the median follow-up time was 14.6 months, 86 pts. had died and 90 had progressive disease. The objective response rate was 22/59 (37.3%). Response of prostate-specific antigen (≥50%) was observed in 48/96 (50%) patients. Median progression-free survival (PFS) was 7.2 months (CI 95% 6.3, 8.1) and median OS was 15.6 months (CI 95% 11.6, 19.7). The most common reversible grade 3/4 toxicity was leukopenia/ neutropenia (39.6/33.3%). Median free testosterone levels were 0.63 pg/ml before and <0.18 pg/ml during carboplatin/docetaxel treatment (nadir levels, p < 0.001; detection limit <0.18 pg/ml). Median serum androgene levels (T + DHT) were 0.1 ng/ml before and below the detection limit of <0.05 ng/ml during DC treatment. In multivariate analyses, LDH, PSA response, free testosterone nadir levels below the detection limit (<0.18 pg/mL) during DC treatment were associated with longer OS (p < 0.05). These data suggest that carboplatin plus weekly docetaxel may be an important second-line treatment option for DRPC patients by inhibiting the testosterone biosynthesis.