Background: Recent data suggest that carboplatin plus weekly docetaxel (DC) may be effective in mDRPC. Platinum(II)-complexes have been shown to interfere with steroid biosynthesis lowering testosterone levels by inhibiting the cholesterol side chain cleavage enzyme (CYP11A1), 3β-hydroxysteroid dehydrogenase (HSD3B1,2) and 17α hydroxylase/C17,20-lyase (CYP17A1). Methods: 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 (q4w), 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. Free testosterone levels were measured before (n=59) and during DC chemotherapy (n=52). Results: Of the 84 pts. treated since February 2005, 95.2% had bone, 41.7% lymph node, 27.4% liver and 17.9% lung involvement. At the time of the current analysis, the median follow-up time was 15.1 months, 64 pts. had died and 75 had progressive disease. The objective response rate was 40.0% and the disease control rate 62.0% in the 50 pts. with measureable disease. Response of prostate-specific antigen (≥50%) was observed in 40/84 (47.6%) patients. Median progression-free survival (PFS) for all patients was 6.9 months (CI 95% 6.0, 7.8) and median OS was 17.9 months (CI 95% 12.6, 23.0). The most common reversible grade 3/4 toxicity was leukopenia/ neutropenia (42.9/38.1%). Median free testosterone levels were 0.69 pg/ml before and <0.18 pg/ml during carboplatin/docetaxel treatment (p<0.001; detection limit <0.18 pg/ml). In multivariate analyses, LDH, number of radiation treatments, PSA response, free testosterone nadir levels, and total androgene nadir levels during DC treatment were associated with longer OS (p<0.05).Conclusions: These data suggest that DC may be an important second-line treatment option for DRPC patients by inhibiting the testosterone biosynthesis.