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Four drug adjuvant chemotherapy with capecitabine improves breast cancer survival

Author: Tamer M. Fouad, M.D. | Submitted: January 03, 2010. Updated: January 03, 2010.

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Joensuu et al published an interesting study1 in which they randomized 1500 women with axillary node-positive or high-risk node-negative breast cancer, in an open-label trial, to either three cycles of capecitabine and docetaxel followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (capecitabine group, n=753) or to three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (control group, n=747). The primary endpoint was recurrence-free survival.1

The recurrence-free survival at 3 years (planned interim analysis) was found to be better with the capecitabine regimen than with control (93% vs 89%; hazard ratio 0∙66, 95% CI 0∙47–0∙94; p=0∙020). Obviously the results stir some controversy and the trial requires longer follow up and further confirmation in a larger setting.

In an accompanying editorial2, Dr. Ruth O’Regan of Emory Winship Cancer Institute, poses some interesting points. Although, capecitabine had been shown to be inferior in previous trials involving elderly patients to regular CMF3, the addition of capecitabine to docetaxel is supported by lab evidence. Capecitabine is known to increase thymidine phosphorylation following docetaxel therapy, which may cause sensitization of cancer cells to capecitabine.

Another interesting finding noted by Joensuu is that ER positive patients seemed to have done better in the capecitabine group. This was also suggested by another trial for metastatic breast cancer in which ER positive patients receiving capecitabine and bevacizumab also did better.4

Dr. Ruth goes on to criticize the “one size fits all” nature of the trial in an era where genetic profiling and molecular subtypes of breast cancer have been clearly shown to have different outcomes. Regardless of the criticism, this trial is valuable in that it suggests the possibility of new more effective combinations using capecitabine with docetaxel in ER positive patients.

Tamer M. Fouad, M.D.. Four drug adjuvant chemotherapy with capecitabine improves breast cancer survival. Doctors Lounge Website. Available at: Accessed May 24 2016.


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