Phase I study of docetaxel plus ifosfamide in patients with advanced cancer

The aim of this study was to determine the maximum tolerated dose of a fixed dose of docetaxel when combined with continuous infusion fosfamide, with and without G-CSF support, in the treatment of advanced cancer, and to evaluate antitumour activity of this combination. Thirty-one patients with advanced malignancies were treated with docetaxel 75 mg/m(2) intravenously on days 1, and fosfamide at increasing dose levels from 1500 mg/m(2)/day to 2750 mg/m(2)/day as a continuous infusion from day 1 - 3, every 3 weeks, A total of 107 cycles of treatment were administered. Without G-CSF support dose-limiting toxicity of grade 4 neutropenia greater than 5 days duration occurred at dose level 1, With the addition of G-CSF the maximum tolerated dose was docetaxel 75 mg/m(2) on day 1 and ifosfamide 2750 mg/m(2)/day on days 1 - 3. Dose limiting toxicity (DLT) included fosfamide-induced encephalopathy, febrile neutropenia and grade three mucositis. Three complete responses and 3 partial responses were seen. This combination of docetaxel and infusional fosfamide is feasible and effective, The recommended dose for future phase II studies is docetaxel 75 mg/m(2) on day 1 and ifosfamide 2500 mg/m(2)/day continuous infusion on days 1 - 3. (C) 2002 Cancer Research UK.