Docetaxel versus mitoxantrone as first-line chemotherapy for hormone-refractory prostate cancer (HRPC) patients. A meta-analysis of 3-year overall survival results

Abstract

4634 Background: Docetaxel (DTX) based chemotherapy is considered the standard treatment for metastatic HRPC patients (pts), with a median survival advantage of 2 months, compared to mitoxantrone (MT). DTX advantage at long term is not defined and further evaluations are needed. Methods: We conducted a meta-analysis to assess the effect of DTX chemotherapy (CT) on overall survival (OS) compared to MT for metastatic HRPC pts. OS probabilities at 12, 18, 24, 30 and 36 months, were considered as the endpoints of interest. Subgroups analysis were performed to evaluate the impact on OS of DTX dose intensity (DI), between dose-dense (q1w) and dose-intense (q3w) schedules. Estimates of the effectiveness of CT were expressed as relative risk reduction (RRR), using a fixed effects model. Associated statistics with 95% confidence interval (CI) were calculated based on adjusted number of pts at risk and events (according to the extent of follow-up) using EasyMA software. Results: Three randomized controlled trials comparing DTX with MT-based CT in HRPC pts were selected (Tannock, Petrylak, NEJM 2004; Oudard, JCO 2005). A total of 1807 pts were included, 1092 allocated to DTX and 715 allocated to MT. The follow-up range was 13.9–58.5 months. No differences were found according to Gleason score, performance status and sites of metastasis. Overall analysis demonstrates a significant OS benefit for DTX at any time points, without any significant heterogeneity (Table). There was a significant difference in OS in favor of DTX dose-intense arm comparing to MT, with no OS benefit for DTX dose-dense schedule. The rank test for publication bias were not significant. Conclusions: This meta-analysis shows on a large data set that DTX-based CT significantly reduced the risk of death by 8–21%, a benefit persisting 3 years later after the start of CT. The benefit of DTX over MT was related to DTX schedule and dose-intense model. No significant financial relationships to disclose.