Toxic effects of early adjuvant chemotherapy for breast cancer.

Combination cytotoxic chemotherapy (intravenous cyclophosphamide, methotrexate, and fluorouracil) was administered within 36 h of mastectomy to 368 women with operable breast cancer in a randomised, controlled clinical trial. The control group of 187 patients received either no chemotherapy or conventionally timed chemotherapy. Unpredictable and severe toxic effects were significantly more common in patients aged greater than or equal to 50 who had received at least 80% of the full chemotherapy dose and in patients who had received chemotherapy within 6 h of mastectomy than in other patients. Methotrexate was believed to be the principal cause of these toxic effects, because of potentiation by nitrous oxide anaesthesia. Leucovorin rescue was therefore added to the regimen.