Benefits seen with capecitabine for breast cancer, but tolerability an issue

NEW YORK (Reuters Health) - In a Finnish study of women with moderate to high risk early breast cancer, adding capecitabine to docetaxel and cyclophosphamide plus epirubicin reduced breast cancer recurrence but was frequently discontinued due to adverse effects.

"Most patients could take the planned six cycles of capecitabine-containing chemotherapy," Dr. Heikki Joensuu, of Helsinki University Central Hospital, noted in an email to Reuters Health. However, "approximately one woman out of four discontinued capecitabine due to adverse effects."

As reported in the November 10th Online First issue of the Lancet Oncology, the open-label randomized trial involved 1500 women with axillary node-positive or high-risk node-negative early breast cancer. A total of 753 of the women received three cycles of capecitabine and docetaxel followed by three cycles of cyclophosphamide, epirubicin, and capecitabine, and the remaining 747 received three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (the control group).

Two patients in each group were excluded from efficacy analyses due to withdrawal of consent or distant metastases.

In a planned interim analysis conducted after 3 years' median follow up, recurrence-free survival, the primary endpoint, was better in the capecitabine arm than the control arm (93% vs 89%; hazard ratio, 0.66; p = 0.02), the authors report.

According to Dr. Joensuu, "Fifty-four women in the capecitabine-containing arm had their cancer return, or died, compared to 80 women in the non-capecitabine containing arm of the study. Forty-three women in the capecitabine-containing arm experienced distant breast cancer metastases compared to 72 women in the non-capecitabine arm."

"There was a 34% reduction in the risk of cancer recurrence or death for those women treated with the capecitabine-containing combination regimen," Dr. Joensuu told Reuters Health, "but the follow-up time of the study participants is still too short to assess the influence of the capecitabine-containing chemotherapy on survival."

The capecitabine regimen was associated with more cases of grade 3 or 4 diarrhea (6% vs 3%) and hand-foot syndrome (11% vs <1%), whereas the control regimen was associated with 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 arm discontinued planned treatment compared with 3% of patients in the control arm. Four patients in the capecitabine arm and two in the control arm died from potentially treatment-related causes.

In an accompanying Reflection and Reaction article, Dr. Ruth M. O'Regan, of Emory Winship Cancer Institute, Atlanta, says: "Although the findings of this trial are not practice-changing, they 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."

"More importantly," she wrote, "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."

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