Mitoxantrone plus docetaxel vs single agent mitoxantrone in metastatic breast cancer (MBC): Results of a multicenter randomized trial

Abstract

637 Background: The benefits of combination therapy vs less toxic single agent therapy for MBC have not been well defined. This prospective, randomized, multicenter phase IV trial compared mitroxantrone plus docetaxel (MDoc) versus mitroxantrone alone (M) as first-line therapy for MBC. Methods: High-risk, chemotherapy-naïve, patients (pts) with MBC aged <35 years, with liver/lung/other metastases, or disease-free interval <18 months, were randomized to either M (12 mg/m2 q3w) for up to 6 cycles plus Doc (80 mg/m2 q3w) until progressive disease (PD) for up to 6 cycles, or to M (12 mg/m2 q3w) administered until complete response (plus 2 cycles), PD, or a cumulative dose of 160 mg/m2 had been reached. Second-line treatment was determined by each study center. The primary endpoint was overall survival (OS); secondary endpoints were time to progression (TTP), response, Brunner-Score and safety. Results: Between June 1997 and December 2001, 179 pts were randomized to MDoc (n=90) or M (n=89). Pts were observed until the end of 2003. For the intent-to-treat population (n=176; 3 pts excluded because of insufficient data) the median TTP was 8.0 months (95% CI: 7.4−8.9) for MDoc and 4.4 months (95% CI: 3.2−7.3) for M (log-rank test, p=0.01). OS was higher for MDoc compared with M but for the first 18 months after starting therapy only. The 2-year survival rate was the same for both treatment regimens. Median OS was 17.2 months (95% CI: 14.8−20.4) for MDoc vs 15.6 months (95% CI: 12.2−20.3) for M (log-rank test, p=0.84). Conclusions: MDoc increases TTP and is associated with a higher OS rate than M for the first 18 months of therapy. Toxicity results and a comparison of the two treatment regimens using Brunner's modified score of TTP, pt rating of treatment benefit, alopecia, vomiting, and WHO performance status will be available for ASCO 2004. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis; Wyeth Pharma Aventis Pharma Germany Aventis Pharma Germany