EVALUATION OF IFOSFAMIDE PLUS MESNA AS FIRST-LINE CHEMOTHERAPY IN WOMEN WITH METASTATIC BREAST-CANCER

Ifosfamide is an oxazaphosphorine analogue of cyclophosphamide with pr oven activity in breast cancer but substantial urotoxicity. The introd uction of mesna as a uroprotective agent provided a stimulus for reexa mination of ifosfamide for therapy of women with metastatic breast can cer. Twenty women with measurable (18 patients) or evaluable (2 patien ts) disease were entered into a phase II clinical trial of ifosfamide plus mesna as first-line chemotherapy. Ifosfamide was administered i.v . at a dose of 1,800 mg/m(2) in 1 L D5W over 2 h on five consecutive d ays. Mesna was administered i.v. at a dose of 400 mg/m(2) over 15 min immediately before and 1 h after ifosfamide, and then every 4 h for th ree more doses. The last three doses could be given either i.v. or ora lly. The planned cycle length was 28 days. Three patients (15%), all w ith measurable disease, achieved a partial response (95% confidence in terval: 3 to 38%). Median time to progression was 137 days and median survival was 407 days. Toxicities included cumulative myelosuppression and substantial nausea and emesis. Four patients were removed from tr eatment because of toxicity alone and a fifth refused further therapy. We conclude that ifosfamide, plus mesna, as given in this protocol ha s definite but limited antitumor activity and poor tolerability.