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

Authors

null

Christoph Reuter

Department of Hematology, Hemostaseology, Oncology, and Stem Cell Transplantation, Medizinische Hochschule Hannover, Hanover, Germany

Christoph Reuter , Michael A. Morgan , Philipp Ivanyi , Viktor Grünwald , Axel S. Merseburger , Christoph A. J. von Klot

Organizations

Department of Hematology, Hemostaseology, Oncology, and Stem Cell Transplantation, Medizinische Hochschule Hannover, Hanover, Germany, Department of Experimental Hematology, Hannover Medical School, Hannover, Germany, Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany, Medical School of Hannover, Hannover, Germany, Department of Urology, University of Lübeck, Lübeck, Germany, Department of Urology and Urologic Oncology, Medical School Hannover, Hannover, Germany

Research Funding

Other

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.

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Abstract Details

Meeting

2017 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Genitourinary (Prostate) Cancer

Track

Genitourinary Cancer—Prostate, Testicular, and Penile

Sub Track

Prostate Cancer - Advanced Disease

Citation

J Clin Oncol 35, 2017 (suppl; abstr 5039)

DOI

10.1200/JCO.2017.35.15_suppl.5039

Abstract #

5039

Poster Bd #

113

Abstract Disclosures