Gemcitabine/Docetaxel Comparable to Capecitabine/ Docetaxel in Metastatic Breast Cancer

NOTTINGHAM, UNITED K I N G D O M - G e m c i t a b i n e (Gemzar)/docetaxel (Taxotere) and capecitabine(Drug information on capecitabine) (Xeloda)/docetaxel showed similar efficacy against metastatic breast cancer, according to Stephen Chan, DM, MRCP, of Nottingham City Hospital in the United Kingdom (abstract 581). Although efficacy was similar, however, the toxicity profiles were different. Patients receiving gemcitabine(Drug information on gemcitabine)/ docetaxel(Drug information on docetaxel) had significantly fewer nonhematologic toxicities, including hand-foot syndrome, mucositis, and diarrhea. Fewer patients taking gemcitabine discontinued the study due to adverse events. Capecitabine-treated patients had significantly less hematologic toxicity. Dr. Chan reported the results of a European phase III study comparing the two regimens as first-line or second- line treatment for patients with anthracycline-pretreated metastatic breast cancer. The median age was 56 years for the gemcita-bine/docetaxel arm and 53 years for the capecitabine/ docetaxel arm, and patients were well balanced for other characteristics. More than 60% of patients in each arm had liver metastases, and more than 40% had lung metastases. Patients were randomized to receive docetaxel (75 mg/m²) on day 1 and either gemcitabine (1,000 mg/m²) on days 1 and 8 or capecitabine (1,250 mg/m² twice daily) on days 1 to 14. Each cycle was 21 days long. The gemcitabine arm received more total cycles (875) than did the capecitabine arm (758), Dr. Chan reported. The relative mean dose intensity was 73% for the gemcitabine arm vs 60% for the capecitabine arm. Responses Similar Efficacy data are based on 305 patients randomized and evaluable: 153 in the gemcitabine group and 152 in the capecitabine group (Table 1). Median progression-free survival, which was the primary objective of the study, was 35 weeks for both treatment groups. Overall response rates were 32% in both treatment arms (P = .9332). Time to treatment failure was 19 weeks in the gemcitabine group vs 18 weeks in the capecitabine group (P = .5056). Nonhematologic Toxicities Safety data were based on 302 patients who were randomized and received treatment. Grade 3/4 hematologic toxicities were similar, with neutropenia and leukopenia being the most common for both regimens. For nonhematologic toxicities, however, although there were no incidences of grade 3/4 hand-foot syndrome in the gemcitabine group, there were 39 cases (26%) in the capecitabine group. Grade 3/4 diarrhea was also more pronounced in the capecitabine group, occurring in 25 patients (17%) vs 11 patients (7%) in the gemcitabine group. Mucositis was experienced by 20 patients (13%) in the capecitabine group vs 6 patients (4%) in the gemcitabine group. More serious adverse events occurring in the capecitabine group led to drug-related discontinuation of therapy in 42 patients (28%) in the capecitabine group vs 20 patients (13%) in the gemcitabine group. "Gemcitabine, capecitabine, and docetaxel are all highly active agents in anthracycline-pretreated metastatic breast cancer. We believed that a comparison of gemcitabine and capecitabine, each combined with docetaxel, would provide valuable information for clinicians in choosing an optimal treatment," Dr. Chan said. The principal investigator for the study was Pierre Fumoleau, MD, of the Centre Rene Gauducheau, nantes-Saint Herblain, Herblain, France. More Clinically Acceptable Capecitabine Dose Tested In a discussion of Dr. Chan's pre sentation, Andrew D. Seidman, MD, of the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center, acknowledged that the gemcitabine/ docetaxel doublet was associated with less toxicity, whereas the regimens were "indistinguishable" with respect to efficacy. Dr. Seidman pointed out that the capecitabine dose in this study is the established dose and the dose for which efficacy has been demonstrated, but it is not well tolerated by many patients, and therefore dose reductions are often necessary. "Perhaps the more relevant and robust question addressing the optimal application of these agents in metastatic breast cancer" is asked in an ongoing international trial, Dr. Seidman said, "where patients with cancer progressing on gemcitabine/ docetaxel cross over to capecitabine and patients with progression on capecitabine/docetaxel cross over to gemcitabine. Of note, this trial incorporates what many clinicians feel is a more clinically acceptable 20% lower dose of capecitabine as a component of this doublet, as compared with the Chan trial." The dose of capecitabine in this international trial is 2,000 mg/m² in divided doses on 14 of the 21 days in the cycle.