FEASIBILITY TRIAL OF HIGH-DOSE 7-DAY CONTINUOUS-INFUSION IFOSFAMIDE GIVEN ON AN OUTPATIENT BASIS

High-dose ifosfamide (HD-IFX) has shown significant antitumor activity in advanced sarcoma and breast carcinoma. The use of uroprotective ag ents and the availability of ambulatory continuous-infusion pumps has allowed dose escalation in the administration of ifosfamide (IFX) on a n outpatient schedule. We report the results of a phase II trial of IF X given at high doses to heavily pretreated patients. IFX was infused at 2 g/m(2) per day for a total of 7 days through a central venous acc ess, with cycles being repeated every 21 days. Mesna was given concomi tantly at equimolar doses. No hematopoietic support was used. A total of 27 heavily pretreated patients whose disease had progressed during conventional-dose chemotherapy were included (14 sarcomas, 10 breast c arcinomas, and 3 bladder carcinomas). Reversible neutropenia and gastr ointestinal toxicity were the most frequently encountered toxicities. Only two patients developed transient renal failure, and two others de veloped central nervous system toxicity. No treatment-related death wa s observed. Of 22 patients who were evaluable for response, 6 (27%) sh owed an objective response (OR), all ORs being partial responses (PRs) with a median duration of 6 months, and 12 patients had stable diseas e (SD; 55%) with a median duration of 3.5 months. The median overall s urvival (OS) was 6 months. Three patients underwent high-dose chemothe rapy after showing a response to our IFX schedule. We conclude that co ntinuous-infusion IFX given in an out-patient setting is a feasible an d active regimen that produces, a manageable toxicity profile in heavi ly pretreated breast cancer and sarcoma patients. Early institution of this schedule in less advanced stages could improve the results obtai ned.