Gemcitabine-oxaliplatin plus prednisolone is active in patients with castration-resistant prostate cancer for whom docetaxel-based chemotherapy failed

J-L Lee; J-H Ahn; M K Choi; Y Kim; S-W Hong; K-H Lee; I-G Jeong; C Song; B-S Hong; J H Hong; H Ahn

doi:10.1038/bjc.2014.204

Gemcitabine-oxaliplatin plus prednisolone is active in patients with castration-resistant prostate cancer for whom docetaxel-based chemotherapy failed

Br J Cancer. 2014 May 13;110(10):2472-8. doi: 10.1038/bjc.2014.204. Epub 2014 Apr 15.

Authors

J-L Lee¹, J-H Ahn¹, M K Choi², Y Kim², S-W Hong², K-H Lee³, I-G Jeong⁴, C Song⁴, B-S Hong⁴, J H Hong⁴, H Ahn⁴

Affiliations

¹ 1] Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, Korea [2] Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, Korea.
² Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, Korea.
³ Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, Korea.
⁴ Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, Korea.

Abstract

Background: There has been no previous study on the activity of gemcitabine in combination with oxaliplatin (GemOx) for castration-resistant prostate cancer (CRPC).

Methods: The GemOx was preclinically tested for cytotoxic activity in human prostate cancer cell lines. Clinically, patients with CRPC who failed prior docetaxel were treated with gemcitabine 1000 mg m(-2) and oxaliplatin 100 mg m(-2) intravenously every 2 weeks and prednisolone 5 mg orally twice daily. The primary end point was the prostate-specific antigen (PSA) response rate.

Results: The GemOx displayed synergistic effects based on Chou and Talalay analysis. In the phase II study, 33 patients were accrued. The median dose of docetaxel exposure was 518 mg m(-2). A total of 270 cycles were administered with a median of eight cycles per patient. A PSA response rate was 55% (95% CI, 38-72) and radiologic response rate was 82% (9 out of 11). With a median follow-up duration of 20.5 months, the median time to PSA progression was 5.8 months (95% CI, 4.4-7.2) and the median overall survival was 17.6 months (95% CI, 12.6-22.6). The most frequently observed grade 3 or 4 toxicities were neutropenia (13%) and thrombocytopenia (13%).

Conclusions: The GemOx is active and tolerable in patients with metastatic CRPC after docetaxel failure (NCT 01487720).

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / blood
Adenocarcinoma / drug therapy*
Adenocarcinoma / radiotherapy
Adenocarcinoma / secondary
Aged
Aged, 80 and over
Antineoplastic Agents, Hormonal / pharmacology
Antineoplastic Agents, Hormonal / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Cell Line, Tumor / drug effects
Combined Modality Therapy
Deoxycytidine / administration & dosage
Deoxycytidine / adverse effects
Deoxycytidine / analogs & derivatives
Deoxycytidine / pharmacology
Disease-Free Survival
Docetaxel
Drug Resistance, Neoplasm
Drug Synergism
Gemcitabine
Humans
Infusions, Intravenous
Inhibitory Concentration 50
Kaplan-Meier Estimate
Male
Middle Aged
Neutropenia / chemically induced
Organoplatinum Compounds / administration & dosage
Organoplatinum Compounds / adverse effects
Organoplatinum Compounds / pharmacology
Oxaliplatin
Prednisolone / administration & dosage
Prednisolone / adverse effects
Prostate-Specific Antigen / blood
Prostatic Neoplasms / blood
Prostatic Neoplasms / drug therapy*
Prostatic Neoplasms / pathology
Prostatic Neoplasms / radiotherapy
Salvage Therapy*
Taxoids / pharmacology
Taxoids / therapeutic use
Thrombocytopenia / chemically induced
Treatment Outcome

Substances

Antineoplastic Agents, Hormonal
Organoplatinum Compounds
Taxoids
Oxaliplatin
Deoxycytidine
Docetaxel
Prednisolone
Prostate-Specific Antigen
Gemcitabine