Activity of ifosfamide in breast cancer

Ifosfamide is an alkylating agent that has clearly demonstrated efficacy against advanced breast cancer. In broad phase II trials, ifosfamide produced response rates of approximately 15% to 20%, and up to 30% in patients without exposure to previous chemotherapy. In subsequent studies, in which ifosfamide was evaluated in higher doses with mesna uroprotection in advanced breast cancer patients with or without prior chemotherapy, the combined complete and partial response rate was 28%. Ifosfamide has also been used in combination regimens. The ifosfamide/methotrexate/5-fluorouracil (IMF) combination has produced efficacy similar to that of the cyclophosphamide/methotrexate/5-fluorouracil (CMF) combination in both previously treated and untreated metastatic breast cancer. Combinations of ifosfamide/epirubicin, ifosfamide/mitoxantrone, and ifosfamide/etoposide have shown encouraging results. Response rates of approximately 70% have been obtained with regimens that include ifosfamide/doxorubicin or ifosfamide/epirubicin. The dose-limiting toxic reactions of ifosfamide, with administration of mesna uroprotection, are myelosuppression, renal tubular acidosis, and renal insufficiency. Additional studies are needed to determine the role of ifosfamide in well-defined patient subsets, to assess its cross-resistance with other alkylating agents, and to determine the slope of the dose-response curve in patients with breast cancer. Further, the role of ifosfamide in front-line combinations needs to be defined.