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Carboplatin plus weekly docetaxel as salvage chemotherapy in docetaxel-resistant and castration-resistant prostate cancer (DRPC).

172 Background: Cabacitaxel has recently been approved by the FDA as second-line chemotherapy for patients progressing during or after first-line docetaxel chemotherapy. However, cabacitaxel treatment is hampered by high costs and toxicity. Carboplatin in combination with docetaxel may also be effective in DRPC. Platinum(II)-complexes have been shown to lower 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, 55 consecutive DRPC pts 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 2×5mg/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 and during carboplatin/docetaxel chemotherapy (n=25).


RESULTS
Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 28/55 (50.9%) patients. At the time of the current analysis the median follow-up time was 11.9 months and 32/55 patients had died. Median progression-free survival (PFS) for all patients was 7.5 months (CI 95% 5.7, 9.3) and median overall survival (OS) was 17.1 months (CI 95% 10.3, 23.9). In PSAR, PFS was 13.6 (CI 95% 7.8, 19.4) months versus 4.3 (CI 95% 2.9, 5.7) months in PSANR (p<0.001; hazard ratio HR 0.159) and OS was 24.4 months (CI 95% 18.1, 30.8) versus 8.1 (CI 95% 3.4, 12.8) months (p<0.001; HR 0.208). This regimen was reasonably well tolerated, with leukopenia/neutropenia as the most common reversible grade 3/4 toxicity (44.2/40.4%). Median free testosterone levels were 1.05 pg/ml before and 0.26 pg/ml during carboplatin/docetaxel treatment (p<0.01).


CONCLUSIONS
Our data suggest that carboplatin/docetaxel may be an important therapeutic second-line treatment option for DRPC patients by inferfering with the testosterone synthesis. No significant financial relationships to disclose.