Abstract 5382
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 = 82) and during carboplatin/docetaxel chemotherapy (n = 76).
Results
Of the 106 pts. treated since February 2005, 96.2% had bone and 63.2 % soft tissue metastases ( 45% lymph node, 27% liver and 21% lung involvement). At the time of the current analysis, the median follow-up time was 13.5 months, 101 pts. had died and 102 had progressive disease. The objective response rate was 43.2% and the disease control rate 64.2% in the 67 pts. with measureable disease. Response of prostate-specific antigen (≥50%) was observed in 50 patients (47.1%). Median progression-free survival (PFS) for all patients was 6.9 months (CI 95% 5.7, 8.0) and median OS was 14.1 months (CI 95% 10.9, 17.3). The most common reversible grade 3/4 toxicity was leukopenia/ neutropenia (40.5/32.1%). Median free and total testosterone levels were reduced below the detection limit during DC treatment (from 0.55 pg/ml to < 0.18 pg/ml and 0.08 to < 0.05 ng/ml, respectively). Testosterone nadir values <0.18 pg/ml during DC treatment were associated with longer PFS, OS and post-hoc OS (p < 0.05).
Conclusions
These data suggest that carboplatin plus weekly docetaxel may be an important second-line treatment option for DRPC patients by inhibition the testosterone biosynthesis.
Clinical trial identification
Legal entity responsible for the study
Christoph Reuter.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
C.W.M. Reuter: Advisory board: Eisai, Bayer, Tesaro, Sanofi, Astellas, Janssen. All other authors have declared no conflicts of interest.
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