Xeloda (capecitabine) plus docetaxel combination therapy in locally advanced/metastatic breast cancer: Latest results

Background: Xeloda (X) is a thymidine phosphorylase (TP)-activated oral fluoropyrimidine with high single-agent activity in metastatic breast cancer. Docetaxel (D) is highly active in breast cancer and upregulates TP, leading to synergistic activity with X. Methods: 511 patients with anthracycline-pretreated locally advanced/metastatic breast cancer were randomized to 21-day cycles of either combination therapy (X 1250mg/m² bid, d1-14 plus D 75mg/m², d1; n=255) or monotherapy (D 100mg/m², dl; n=256). The primary efficacy endpoint is TTP. In the first report of this trial [O'Shaughnessy et al SABCS 2000:A381] overall survival was significantly superior with X+D, with median survival of 13.7 vs 11.1 months, respectively. We report here the latest results. Results: Minimum follow-up is now 15 months. X+D resulted in significantly superior OS (HR=0.775 [95% CI: 0.63-0.95], p=0.0126, median 14.5 vs 11.5m with monotherapy), TTP (HR=0.652 [95% CI: 0.54-0.77], p=0.0001, median 6.1 vs 4.2m), and RR (42 vs 30%, p=0.006). Treatment-related adverse events (AE) occurred in 98% and 94% of the X+D and D arms, respectively. Patients receiving X+D experienced a higher incidence of gastrointestinal AE and hand-foot syndrome, whereas there was more neutropenic fever, arthralgia and pyrexia in the monotherapy group. Grade 4 AE were less common with X+D (25% vs 30%, due to neutropenic fever in the D arm). Grade 3 AE were more common in the X+D arm, primarily owing to hand-foot syndrome in the second cycle. X+D AE were effectively managed with appropriate medical intervention, treatment interruption and if necessary, dose reduction. Conclusions: X+D therapy offers the unique benefit of superior OS, with a manageable safety profile. It is a highly effective new combination chemotherapy for the treatment of advanced disease.