708 INTERMITTENT CHEMOTHERAPY FOR METASTATIC HORMONE REFRACTORY PROSTATE CANCER: LONG TERM RESULTS OF A PROSPECTIVE RANDOMIZED TRIAL

Abstract

INTRODUCTION AND OBJECTIVES: To evaluate the effect of intermittent vs. continuous docetaxel chemotherapy in metastatic castration-resistant prostate cancer (CRPC) on survival, PSA response, quality of life and toxicity, in a randomized pilot trial prospectively. METHODS: A total of 83 patients underwent randomization from January 2004 to December 2009 between standard continuous therapy arm (SA, n 41) and intermittent therapy arm (IA, n 42). All patients received 75 mg/m2 of docetaxel as a one hour intravenous infusion every 21 days and 2x5 mg oral prednisolone daily. Treatment was planned to continue up to 12 cycles without any break in SA. Patients in IA had a chemotherapy holiday after every 4 cycle until disease progression. Treatment was resumed when the serum PSA was increased by %80 of nadir, or 2 points increase in pain score or appearance of any new metastatic lesions or for other evidence of disease progression. Clinical evaluation regarding PSA, visual analog scale (VAS), quality of life (QLQC30, version 3.0) and disease extent was performed prior to each cycle. Toxicity was graded by CTC-NCI criteria. RESULTS: Mean age, PSA and hemoglobin values for SA and IA were; 67.6 1.3 and 66.2 1.2 years; 244.8 65.4 and 147.4 29.7 ng/ml, 12.3 0.2 and 12.5 0.2 g/dl, respectively (p 0.05). Mean number of chemotherapy cycles for SA and IA were 10.6 0.8 and 9.6 0.8, respectively (p 0.358). PSA response rates following 4, 8, 12 and 16 cycles were 61.9%, 29.4%, 45.5% and 57.1 for SA; 62.8%, 50%, 44.4% and 57.1%, for IA respectively. Median duration of first, second and third treatment holiday were 12 (n 18, range: 4–52), 16 (n 9, range: 6–34) and 14 (n 3, range: 12–15) weeks in IA, respectively. Mean time to treatment failure for SA and IA were 15.5 6.6 and 12.7 3.7 months, respectively (p 0.496). Two-years overall survival rate for SA and IA was similar (58.7% vs. 52.9%), median survival of patients in SA and IA was 30.4 4.5 (95%CI 21.6–39.2) and 27 2.8 (95% CI 21.5– 32.5) months, respectively (log rank p 0.879). The quality of life parameters were not altered significantly. Most frequent grade 3–4 adverse events in decreasing order were; alopecia, changes in taste sensation and flushing which were observed at similar rates in both arms. None of the patients required cessation of the applied protocol due to toxicity. CONCLUSIONS: Present study with a limited sample size states that the intermittent chemotherapy is a suitable alternative for all patients with CRPC. Future studies are necessary to precisely define the strategy for intermittent chemotherapy in CRPC.