Addition of capecitabine to standard chemotherapy regimen increased recurrence-free survival

The addition of capecitabine to a chemotherapy regimen containing standard agents reduced the incidence of breast cancer recurrence but yielded a higher rate of discontinuance because of adverse effects.

Researchers conducted an open-label trial in which 1,500 women with axillary node–positive or high-risk node-negative breast cancer were randomly assigned to three cycles of capecitabine (Xeloda, Hoffmann La Roche) and docetaxel followed by three cycles of cyclophosphamide, epirubicin and capecitabine (n=753) or to three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin and fluorouracil (n=747). The researchers excluded two patients from each group after they withdrew consent or because of distant metastases.

Median follow-up was 35 months. Three-year recurrence-free survival was 93% for patients assigned to the capecitabine regimen vs. 89% for those assigned to standard agents only (P=.020). Patients assigned to the capecitabine regimen experienced more cases of grade-3 or -4 diarrhea (6% vs. 3%) and hand–foot syndrome (11% vs. <1%). Patients assigned to the standard-agent regimen reported more cases of grade-3 or -4 neutropenia (98% vs. 86%) and febrile neutropenia (9% vs. 4%).

Twenty-four percent of patients in the capecitabine group discontinued treatment compared with 3% of patients in the standard-agent regimen group. Four patients assigned to the capecitabine regimen and two assigned to the standard-agent regimen died from causes that the researchers said were potentially treatment related.

In an accompanying “Reflection and Reaction” piece, Ruth M. O’Regan, MD, of the department of hematology and medical oncology at Emory Winship Cancer Institute in Atlanta, said these findings are not practice changing but are “intriguing and could merit further assessment in a larger trial.

“However, the significant toxicity noted with the addition of capecitabine to the taxane–anthracycline backbone dampens enthusiasm for further studies of this approach,” O’Regan added. “More importantly, it is imperative that we take a more rational approach to the treatment of early-stage breast cancer by tailoring our treatment approaches to molecular phenotypes.”

Joensuu H. Lancet Oncol. 2009;doi:10.1016/S1470-2045(09)70307-9.