New chemotherapy combo produces side effects, but no extra efficacy, in early breast cancer patients

Professor Gunter von Minckwitz, Chairman of the German Breast Group, Neu-Isenberg, Germany, and his team set out to look at the use of the combination in early breast cancer. “We recruited 1510 patients with previously untreated primary tumours,” he said. “Each received the normal preoperative treatment of four cycles of epirubicin and cyclophosphamide. We then randomised them to either four cycles of docetaxel alone, four cycles of simultaneous docetaxel and capecitabine, or four cycles of docetaxel followed by four cycles of capecitabine. If capecitabine were to improve outcomes, we wanted to see how best to use it – simultaneously or in sequence.”

The scientists planned to study the pathologic response at surgery – the way, if any, in which the tumour had reacted to the administration of the chemotherapy drug.

“However, we found no difference in efficacy between the three arms of the trial with regard to pathologic response, clinical response, and rate of breast conservations,” said Professor von Minckwitz. “The overall rate of pathologic complete responses (pCRs) – no cancer in the breast or lymph nodes – was 29.7%.”

Nor did the length of treatment appear to make a statistically significant difference. What the scientists did find was that the addition of capecitabine to the chemotherapy regime produced more non-haematological toxicities – for example hand-foot syndrome, a skin reaction that appears on the palms of the hands and soles of the feet, and which can be very painful if untreated. They also found increased rates of nail changes, stomatitis (inflammation of the mucous lining the mouth and throat), and diarrhoea.

The scientists now intend to follow up their work by correlating the response at the time of surgery with the long-term outcomes for patients. “Although it is the best indication we have at present, it is still uncertain whether pCR is a reliable predictor of long-term activity,” said Professor von Minckwitz.

Given the lack of extra efficacy of adding capecitabine to docetaxel, and the additional toxicities that it produces, the scientists say that they would not recommend using it as preoperative treatment in early breast cancer. “Prolongation of chemotherapy also has the effect of reducing patient compliance, so, given all these factors we would recommend staying with current standard treatments – epirubicin and cyclophosphamide followed by a taxane, or TAC, another commonly used three-drug combination of docetaxel, doxorubicin and cyclophosphamide,” said Professor von Minckwitz.