Abstract
Purpose.To define the maximally tolerated dose (MTD) of ifosfamide when given with G-CSF on an every other week schedule, and to define the MTD of edatrexate that can be given every two weeks with an intense schedule of ifosfamide.Patients and Methods.Forty-one patients with metastatic or unresectable, locally advanced sarcoma participated in this 2-step phase I trial.The starting dose of ifosfamide was 10 gm/m2given by continuous intravenous infusion over 4 days every 2 weeks.When the MTD was defined, edatrexate, beginning at a dose of 40 mg/m2intravenously every 2 weeks was added in subsequent cohorts of patients.Results.Myelosuppression was the most prominent toxicity. Fatigue, nausea, and vomiting were observed in the majority of patients. Ifosfamide 12 gm/m2given every 2 weeks approached or exceeded the MTD. Edatrexate 100 mg/m2could be given safety as an intravenous bolus with ifosfamide 10 gm/m2every 2 weeks. Therapeutic responses were observed in patients with measurable disease.Conclusions.This study demonstrates the feasibility of administering a dose-intense schedule of ifosfamide alone or ifosfamide with edatrexate that might be applied in the adjuvant or neo-adjuvant setting.