Background: Carboplatin plus docetaxel 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 2 cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel (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 (FT) levels were measured before (n = 70) and during CD chemotherapy (n = 62). Results: Of the 93 pts. treated since February 2005, 95.7% had bone, 41.9% lymph node, 26.9% liver and 19.4% lung metastases. At the time of the current analysis, the median follow-up time was 15.4 months. The objective response rate was 38.6% and the disease control rate 71.4% in the 57 pts. with measureable disease. Response of prostate-specific antigen ( ≥ 50%) was observed in 46/93 (49.5%) patients. Median PFS was 7.2 months (CI 95% 6.2, 8.1) and median OS was 15.6 months (CI 95% 11.5, 19.8). The most common reversible grade 3/4 toxicity was leukopenia/ neutropenia (40.0/38.1%). Median FT levels were 0.65 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, FT nadir levels below the detection limit ( < 0.18 pg/mL) during CD treatment were associated with longer OS (p < 0.05). Conclusions: These data suggest that CD may be an important second-line treatment option for mDRPC patients by inhibiting the testosterone biosynthesis.