Prognostic value of free testosterone (FT) levels during chemotherapy with carboplatin plus weekly docetaxel in metastatic castration- and docetaxel-resistant prostate cancer (mDRPC).

Abstract

5039 Background: Carboplatin plus docetaxel (DC) may be effective in mDRPC. Platinum(II)-complexes 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 = 77) and during DC chemotherapy (n = 69). Results: Of the 100 pts. treated since February 2005, 96% had bone metastases, 45% had lymph node, 27% liver and 21% lung involvement. At the time of the current analysis, the median follow-up was 13.6 months, 93 pts. had died and 97 had progressive disease. The objective response rate was 36.5% in the 63 pts. with measureable disease. Response of prostate-specific antigen (≥50%) was observed in 50% of patients. Median progression-free survival (PFS) for all patients was 6.9 months (CI 95% 5.5, 8.3) and median OS was 15.4 months (CI 95% 11.5, 19.4). The most common reversible grade 3/4 toxicity was leukopenia/ neutropenia (40/32%). Median free testosterone levels were 0.61 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, free testosterone nadir levels below the detection limit ( < 0.18 pg/mL) during DC treatment were associated with longer OS (p < 0.05). Conclusions: These data suggest that carboplatin plus weekly docetaxel may be an important salvage treatment option for DRPC patients.