908P - Prognostic value of free testosterone (FT) levels during salvage chemotherapy with carboplatin plus weekly docetaxel in metastatic castration- and d...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Anticancer Agents
Prostate Cancer
Therapy
Biological Therapy
Presenter Christoph W.M. Reuter
Authors C.W.M. Reuter1, M.A. Morgan1, M. Fenner1, V. Grünwald2, A. Ganser1
  • 1Hematology, Hemostasis, Oncology And Stem Cell Transplantation, Hannover Medical School, 30625 - Hannover/DE
  • 2Clinic For Hematology, Hemostasis, Oncology, Hannover Medical School, 30625 - Hannover/DE

Abstract

Background

Recent data suggest that carboplatin plus weekly docetaxel (DC) is an effective salvage therapy in DRPC. Carboplatin, docetaxel and steroids all interfere with testosterone biosynthesis and/or metabolism. In this study the impact of DC treatment on testosterone serum levels was analyzed.

Methods

Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 71 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/m 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. FT was measured before (n = 44) and during carboplatin/docetaxel chemotherapy (n = 38).

Results

Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 34/71 (47.9%) patients. At the time of the current analysis the median follow-up time was 14.5 months and 47/71 patients had died. Median progression-free survival (PFS) for all patients was 6.9 months (CI 95% 4.3, 13.6) and median overall survival (OS) was 18.0 months (CI 95% 10.4, 25.6). Median FT serum levels were 3.0 pmol/L before (n = 43) and below the RIA detection limit of <0.6 pmol/L during carboplatin/docetaxel treatment (testosterone nadir; n = 38; p = 0.011). While only 3/43 patients (pts.) had FT levels <0.6 pmol/L before treatment, in 19/38 pts. FT was <0.6 pmol/L (p < 0.001) during DC treatment. Similarly, median total androgen (TA, testosterone and dihydrotestosterone) serum levels were 0.7 nmol/L before (n = 22) and below the RIA detection level of <0.17 nmol/L during DC treatment (n = 32; p = 0.003). FT levels <0.6 pmol/L during DC treatment were associated with higher PFS (hazard ratio HR 0.39; CI 0.18, 0.83, p = 0.015) and OS (HR 0.15; CI 0.04, 0.55, p = 0.004). 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 (38.0/35.2%).

Conclusion

These data demonstrate for the first time that testosterone is an important prognostic factor for PFS and OS in mDRPC patients receiving chemotherapy.

Disclosure

C.W.M. Reuter: Minor consulting fees from Sanofi Aventis, Amgen,

V. Grünwald: Consulting fees from Novartis,

All other authors have declared no conflicts of interest.