Evaluation of dose-intense ifosfamide, with and without edatrexate, in adults with sarcoma

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 mg/m² given by continuous intravenous infusion over 4 days every 2 weeks. When the MTD was defined, edatrexate, beginning at a dose of 40 mg/m² intravenously 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/m² given every 2 weeks approached or exceeded the MTD. Edatrexate 100 mg/m² could be given safety as an intravenous bolus with ifosfamide 10 gm/m² every 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.