Background: Recent data suggest that carboplatin may be effective in combination with docetaxel in DRPC. Platinum(II)-complexes interfere with steroid biosynthesis, lowering testosterone levels by inhibiting 3β-hydroxysteroid dehydrogenase and 17α hydroxylase (Schertl et al. J Cancer Res Clin Oncol. 2007;133:153-67). Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 59 consecutive DRPC pts gave informed consent and were treated with 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 until disease progression or occurrence of intolerable adverse effects. Efficacy was measured following PCWG2 recommendations. Free testosterone levels were measured before and during carboplatin/docetaxel chemotherapy. Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 29/59 (49.2%) patients. At the time of the current analysis, the median follow-up time was 12.9 months and 36/59 patients had died. Median progression-free survival (PFS) for all patients was 7.2 months (CI 95% 6.1, 8.4) and median overall survival (OS) was 18.6 months (CI 95% 11.6, 25.6). In PSAR, PFS was 15.7 (CI 95% 7.3, 24.1) months and OS was 27.0 months (CI 95% 20.4, 33.6). This regimen was reasonably well tolerated, with leukopenia/neutropenia as the most common reversible grade 3/4 toxicities (44.2/40.4%). Median free testosterone levels were 1.15 pg/ml before and 0.255 pg/ml during carboplatin/docetaxel treatment (testosterone nadir; n=24; p<0.01). While free testosterone levels before DC treatment were associated with lower PSAR (HR 5.582 CI 1.105, 28.195; p=0.037), free testosterone levels <0.3 pg/ml during DC treatment were associated with higher PSAR, PFS and OS (HR 11.7 CI 1.49, 91.5; HR 0.2 CI 0.05, 0.78; HR 0.129 CI 0.02, 0.8; p<0.03, respectively). Conclusions: These data suggest that carboplatin plus weekly docetaxel may be an important second-line treatment option for DRPC patients by inhibiting testosterone biosynthesis.