On the safety of perioperative adjuvant chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil in breast cancer.

Combination cytotoxic chemotherapy (intravenous cyclophosphamide, methotrexate and 5-fluorouracil) was administered within 36 h of mastectomy to 1629 eligible women with operable breast cancer in a randomized controlled clinical trial. Previously reported unpredictable and severe toxic effects were probably due to an interaction between methotrexate and nitrous oxide used in anesthesia. The addition of intravenous 5-formyl-tetrahydrofolate (Leucovorin) and intensification of postoperative monitoring of patients have decreased toxic effects and enhanced the safety of the chemotherapy regimen.