Sheng-Chun Hung1,2, Li-Wen Chang1,2, Jian-Ri Li1,2,3, Shian-Shiang Wang1,2,4, Cheng-Kuang Yang1, Chuan-Shu Chen1,2, Kevin Lu1,5, Cheng-Che Chen1, Shu-Chi Wang1, Chia-Yen Lin1,2, Chen-Li Cheng1,2, Yen-Chuan Ou1,2,6,7, Kun-Yuan Chiu8,4. 1. Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C. 2. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. 3. Department of Medicine and Nursing, Hungkuang University, Taichung, Taiwan, R.O.C. 4. Department of Applied Chemistry, National Chi Nan University, Nantou, Taiwan, R.O.C. 5. School of Medicine, National Yang Ming University, Taipei, Taiwan, R.O.C. 6. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C. 7. Department of Urology, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan, R.O.C. 8. Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.; chiu37782002@yahoo.com.
Abstract
BACKGROUND/AIM: Docetaxel has been widely used in metastatic Castration-resistant Prostate Cancer (mCRPC) patients for decades. The purpose of the study was to evaluate the efficacy of docetaxel rechallenge in patients with mCRPC. PATIENTS AND METHODS: We retrospectively compared patients who had received either first-line docetaxel and rechallenge after Androgen Receptor-axis Targeted therapies (ARAT), to those without rechallenge docetaxel. Multivariate cox-regression analysis was used to evaluate survival. RESULTS: Out of the 204 patients with mCRPC enrolled in the study, 24 patients received docetaxel rechallenge and 180 did not. The median overall survival was 50.11 months in the rechallenge group, as compared to 26.36 months in the non-rechallenge group (p of log rank=0.044). In the multivariate model, doxetaxel rechallenge was an independent risk factor for overall survival [hazard ratio (HR)=0.59, 95% confidence interval (CI)=0.32-0.99], together with the performance status score 2 (HR=2.46, 95%CI=1.32-4.58), hormone-sensitive state duration (HR=0.99, 95%CI=0.99-0.999), liver (HR=1.90, 95%CI=1.04-3.47) and brain metastases (HR=2.23, 95%CI=1.26-5.46). The advantage of rechallenge was addressed in the androgen receptor-axis-targeted (ARAT) non-responsive patients (HR=0.36, 95%CI=0.17-0.78). Adverse events were at 29.17% with Grade 3/4 neutropenia and at 20.83% with Grade 1/2 neutropenia in the docetaxel rechallenge group. CONCLUSION: The docetaxel rechallenge improved survival in patients with mCRPC failure of first-line docetaxel and subsequent abiraterone acetate or enzalutamide. Independent predictive factors for overall survival included i) the performance status, ii) hormone-sensitive state duration, iii) liver and iv) brain metastases. Patients non-responsive to ARATs will benefit from docetaxel rechallenge with regards to overall survival.
BACKGROUND/AIM: Docetaxel has been widely used in metastatic Castration-resistant Prostate Cancer (mCRPC) patients for decades. The purpose of the study was to evaluate the efficacy of docetaxel rechallenge in patients with mCRPC. PATIENTS AND METHODS: We retrospectively compared patients who had received either first-line docetaxel and rechallenge after Androgen Receptor-axis Targeted therapies (ARAT), to those without rechallenge docetaxel. Multivariate cox-regression analysis was used to evaluate survival. RESULTS: Out of the 204 patients with mCRPC enrolled in the study, 24 patients received docetaxel rechallenge and 180 did not. The median overall survival was 50.11 months in the rechallenge group, as compared to 26.36 months in the non-rechallenge group (p of log rank=0.044). In the multivariate model, doxetaxel rechallenge was an independent risk factor for overall survival [hazard ratio (HR)=0.59, 95% confidence interval (CI)=0.32-0.99], together with the performance status score 2 (HR=2.46, 95%CI=1.32-4.58), hormone-sensitive state duration (HR=0.99, 95%CI=0.99-0.999), liver (HR=1.90, 95%CI=1.04-3.47) and brain metastases (HR=2.23, 95%CI=1.26-5.46). The advantage of rechallenge was addressed in the androgen receptor-axis-targeted (ARAT) non-responsive patients (HR=0.36, 95%CI=0.17-0.78). Adverse events were at 29.17% with Grade 3/4 neutropenia and at 20.83% with Grade 1/2 neutropenia in the docetaxel rechallenge group. CONCLUSION: The docetaxel rechallenge improved survival in patients with mCRPC failure of first-line docetaxel and subsequent abiraterone acetate or enzalutamide. Independent predictive factors for overall survival included i) the performance status, ii) hormone-sensitive state duration, iii) liver and iv) brain metastases. Patients non-responsive to ARATs will benefit from docetaxel rechallenge with regards to overall survival.
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