Capecitabine combo produces side effects

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Adding capecitabine, a drug that inhibits DNA synthesis and slows the growth of tumour tissue, to docetaxel, in patients with early breast cancer, leads to more toxicities and does not improve the efficacy of therapy, a German scientist told the 6th European Breast Cancer Conference (EBCC-6) today (Thursday 17 April). Previously, such a combination had improved patient survival in metastatic disease, where the cancer has spread to other parts of the body.

Professor Gunter von Minckwitz, Chairman of the German Breast Group, Neu-Isenberg, Gera number of, 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 therapy 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 researchers 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 therapy appear to make a statistically significant difference. What the researchers 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 researchers now intend to follow up their work by correlating the response at the time of surgery with the long-term outcomes for patients. Eventhough 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 researchers say that they would not recommend using it as preoperative therapy 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 therapys epirubicin and cyclophosphamide followed by a taxane, or TAC, another usually used three-drug combination of docetaxel, doxorubicin and cyclophosphamide, said Professor von Minckwitz.


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