Capecitabine/Paclitaxel Safe and Effective as First-Line Therapy for Metastatic Breast Cancer

CHICAGO—A capecitabine (Xeloda) plus paclitaxel regimen is effective and safe as first-line treatment of metastatic breast cancer, according to 3-year results of a multicenter, phase II study. Toxicity was manageable, with a relatively low incidence of grade 3/4 adverse events, including hand-foot syndrome. The study, which is among the latest to evaluate the potential for synergy between capecitabine and taxanes, was described by William J. Gradishar, MD, associate professor of medicine at Northwestern University Medical School, Chicago.

All patients in the study received paclitaxel 175 mg/m² on day 1 of a 21-day cycle, along with capecitabine 825 mg/m² twice daily for the first 14 days of that cycle. That is a lower initial capecitabine dose than the 1,250 mg/m² dose used in a previous phase III trial of capecitabine plus docetaxel (Taxotere) for metastatic breast cancer. That dose was also administered twice daily, although dose reduction was allowed for adverse events (O’Shaughnessy J, et al: J Clin Oncol 20: 2812-23, 2002).

"We started at a lower dose of capecitabine, and that actually turned out to be a smart move, because we maintained the activity" previously demonstrated for capecitabine/docetaxel, while potentially limiting toxicity, Dr. Gradishar stated.

Overall Response Rate 51%

The median age of the 47 evaluable patients was 52 years (range 35 to 76 years). Most of the patients were receiving capecitabine/paclitaxel as first-line therapy; only three patients (6%) had received a taxane or anthracycline in the metastatic setting. The median number of treatment cycles was seven.

The overall response rate in the capecitabine/paclitaxel trial was 51.1%. Median time to progression was 10.5 months and median overall survival 20.6 months. The most common grade 3/4 adverse events included seven cases of neutropenia (15%), six cases of alopecia (13%) and five cases of grade 3 hand-foot syndrome (11%).

These findings on the potential utility of a capecitabine/taxane combination corroborate the previously cited phase III study of capecitabine/docetaxel. In that trial, which included more than 500 women with anthracycline-pretreated metastatic breast cancer, capecitabine plus docetaxel resulted in a significantly improved response rate vs docetaxel alone (42% vs 30%), as well as prolonged time to tumor progression (6.1 vs 4.2 months) and overall survival (14.5 vs 11.5 months). Investigators said those results suggest capecitabine/docetaxel is "an important treatment option" for women with anthracycline-pretreated metastatic breast cancer, particularly when considering the manageable toxicity profile. More grade 3 adverse events were seen with combination capecitabine/docetaxel therapy (71% vs 49%) than for docetaxel alone, although grade 4 events were somewhat more common with docetaxel (25% for the combination and 31% for docetaxel alone).

Incidence of hand-foot syndrome was 2% in the first cycle and 13% in the second cycle, comparable to what Dr. Gradishar and colleagues have observed in the phase II capecitabine/paclitaxel trial. "Starting out with that lower dose of capecitabine right from the beginning, there is hand-foot syndrome in the 10% range, and we are not seeing significant (additional) toxicity," Dr. Gradishar said.

Additional Approaches

Capecitabine/paclitaxel is now being considered as a platform for further investigation. One potential approach is augmenting the combination with carboplatin (Paraplatin), due to that agent’s activity and reported synergism with taxanes. Another approach could be to evaluate capecitabine/paclitaxel vs other active regimens in metastatic breast cancer.

"I think it’s even reasonable to think of this combination as a nonanthracycline adjuvant therapy," Dr. Gradishar said. "All of these approaches are in discussion at this point."