Background: Recent data suggest that carboplatin plus weekly docetaxel (DC) may be effective in mDRPC. Carboplatin, docetaxel and steroids interfere with testosterone biosynthesis and/or metabolism. In this study the impact of DC treatment on testosterone blood levels was analyzed. Methods: Docetaxel failure/resistance was defined as disease progression during docetaxel treatment according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 74 consecutive DRPC patients (pts.) were treated with at least 2 cycles of carboplatin AUC5 iv for 30 min on day 1 plus docetaxel at a dose of 35 mg/m2 iv for one hour on days 1, 8, (15) every 4 weeks and prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. FT levels were measured before (n=51) and during DC chemotherapy (n=41). Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 36/74 (48.6%) pts. At the current analysis the median follow-up time was 16.6 months and 56/74 pts. had died. Median progression-free survival (PFS) was 6.9 months (CI 95% 5.9, 7.9) and median overall survival (OS) was 18.6 months (CI 95% 12.4, 24.7). Median nadir FT levels were 2.8 pmol/L before and below the RIA detection limit of 0.6 pmol/L during DC treatment (p=0.008). While only 4/51 pts. had FT levels <0.6 pmol/L before DC treatment (all under abiraterone therapy), 28/41 pts. had nadir FT values <0.6 pmol/L during DC chemotherapy (p<0.0001). Median FT levels <0.9 pmol/L during DC treatment were associated with a higher PSA response rate (hazard ratio HR 0.19; CI 0.05, 0.78, p=0.021) and a higher OS (HR 0.34; CI 0.15, 0.81, p=0.015). FT remained statistically prognostic in multivariable analyses. The DC regimen was reasonably well tolerated, with leukopenia/ neutropenia as the most common reversible grade 3/4 toxicity (41.9/37.8%). Conclusions: These data demonstrate for the first time that FT is an important prognostic factor for PSAR and OS in mDRPC pts. during chemotherapy.