A PHASE-I TRIAL OF IFOSFAMIDE AND PACLITAXEL WITH GRANULOCYTE-COLONY-STIMULATING FACTOR IN THE TREATMENT OF PATIENTS WITH REFRACTORY SOLID TUMORS

BACKGROUND. Ifosfamide and paclitaxel are antineoplastic agents with b road activity and with different mechanisms of action. A Phase I trial was conducted to determine the maximum tolerated dose and associated toxicities of these agents when used in combination. METHODS. Patients with refractory, incurable solid tumors were entered on a 5-step Phas e I trial of ifosfamide, given in doses of 2-3 g/m(2) intravenous (i.v .) bolus for 3 days with mesna support, and paclitaxel, given in doses of 135-190 g/m(2) i.v. by continuous infusion over 24 hours. Paclitax el was given after the first dose of ifosfamide on Day 1. RESULTS. Twe nty-three patients were treated, and the maximum tolerated dose was th e highest planned dose level of the trial: ifosfamide, 3 g/m(2)/day i. v. for 3 days, and paclitaxel, 190 mg/m(2) i.v. over 24 hours. Hematol ogic toxicity was not dose-limiting, and although neutropenia occurred , it was brief (median, 2-4 days) and resulted in hospitalization for neutropenia and fever in only 7 of 111 courses of therapy. For patient s treated at the highest dose level, only 1 of 50 courses of therapy r esulted in hospitalization for neutropenia and fever. Nonhematologic t oxicity also was not severe and no significant neuropathy occurred. Al though patients entered into the study were heavily pretreated, respon ses were observed, particularly in patients with breast or ovarian car cinoma. CONCLUSIONS. Ifosfamide and paclitaxel can be administered saf ely in the doses used in this study and there are indications of signi ficant antitumor effect. Further studies are necessary to explore the antineoplastic activity of this regimen, particularly for patients wit h breast and ovarian carcinoma. (C) 1998 American Cancer Society.