Safety results of a phase III trial evaluating ADT+ docetaxel versus ADT alone in hormone-naïve metastatic prostate cancer patients (GETUG-AFU 15/0403).

Abstract

4681 Background: Androgen deprivation therapy (ADT) is the standard treatment of hormone naïve metastatic prostate cancer (HNMPC). We decided to initiate a phase III multicentre trial to evaluate the additional docetaxel (D) chemotherapy in these populations. Methods: Patients (pts) with HNMPC were randomly assigned to either arm A (ADT plus D: 75mg/m2 q3w, 9 cycles) or arm B (ADT alone). Primary endpoint was overall survival. Secondary endpoints included the toxicity profile of D. Results: From 10/2004 to 12/2008, 385 pts were accrued. Median age was 63 years (43-84), median PSA 26.6 ng/ml (0.1-11900), Gleason score >8: 57%. Median number of applied cycles was 9. Pts were classified according to Glass et al. risk groups as good (48%), intermediate (29%), and poor prognosis (22%). Among the 385 pts, neutropenia grade ≥ 3 was observed in 33%, febrile neutropenia: 7%. After accrual of 215 patients, 3 toxic deaths occurred in arm A, 2 due to neutropenia, 1 due to general impairment. After a safety interim analysis, the independent data monitoring committee recommended systematic use of G-CSF from day 5 to day 10 after each D administration. No subsequent toxic death was observed. Furthermore, in arm A rates of toxicity were observed: G ≧ 3 sexual dysfunction 15%, G ≧ 3 fatigue 7%, G ≧ 3 hot flushes 4%, G ≧ 3 nail changes 3%, G ≧ 3 anemia 2% and G ≧ 3 dyspnea 2%. Other toxicities with ≤1% grade ≥3 toxicity were: alopecia 54%, nausea/vomiting 35%, diarrhea 30%, sensory neuropathy 29%, mucositis 29% and peripheral oedema 29%.In arm B: hot flushes 62% (2% G≥ 3), sexual dysfunction 29% (8% G ≥ 3), anemia 22%, and fatigue 19%. Conclusions: Relative to ADT alone D chemotherapy is associated with a significant increase of toxicity. However, apart from a higher incidence of febrile neutropenia, overall toxicity was comparable to toxicity rates observed in previous studies in metastatic castration resistant prostate cancer patients. Systematic use of G-CSF is recommended in this setting. No significant financial relationships to disclose.