Efficacy and Safety of Carboplatin Plus Paclitaxel as the First-, Second-, and Third-line Chemotherapy in Men With Castration-resistant Prostate Cancer

With growing evidence for homology-directed repair gene defects driving castration-resistant prostate cancer (CRPC) progression, platinum chemotherapy is re-emerging as a reasonable therapeutic option. We compared the efficacy of the carboplatin and paclitaxel regimen as the first-, second-, and third-line chemotherapy for CRPC. Even after docetaxel and cabazitaxel administration, carboplatin and paclitaxel could be offered to patients with CRPC with homology-directed repair gene defects. Introduction: Carboplatin and paclitaxel (CP) had shown moderate efficacy in treating castration-resistant prostate cancer (CRPC) before standard first-line docetaxel chemotherapy became available. Currently, for patients with homology-directed repair gene defects as well as for unselected patients, platinum chemotherapy is administered after all standard treatments have been ineffective. Here, we retrospectively studied the efficacy and safety of CP administered as the first-, second-, and third-line chemotherapy in patients with CRPC. Patients and Methods: A retrospective chart review was performed for 58 patients with CRPC who received CP between 2001 and 2018 in a single institution. Twenty-seven patients received CP as the first-line chemotherapy, 21 as the second-line after docetaxel, and 10 as the third-line after docetaxel and cabazitaxel. Prostate-specific antigen (PSA) responses (> 50% decline of PSA from baseline), progression-free survival, overall survival, and adverse events were examined. Results: PSA responses at any time were 55.6%, 19.0%, and 10.0%; PSA responses at 12 weeks were 48.1%, 14.3%, and 10.0%; the median progression-free survival was 3, 1, and 1 month; and the median overall survival was 19, 11, and 6 months, respectively, for the first-, second-, and third-line settings. The only patient who achieved exceptional and durable PSA response in the third-line setting had a deleterious germline BRCA2 mutation (5645C>A). The adverse event profile was favorable. Conclusion: CP shows moderate efficacy against CRPC in the first-line setting, but shows little effect in the third-line setting. CP after docetaxel and cabazitaxel may be recommended in selected patients with CRPC with homology-directed repair gene defects. (C) 2019 Elsevier Inc. All rights reserved.