Paclitaxel by 72-hour continuous infusion followed by bolus intravenous ifosfamide or epirubicin: Results of two phase I studies

Study Purposes: To determine the maximum-tolerated dose (MTD) of paclitaxel administered by 72-hour continuous infusion followed by bolus intravenous ifosfamide on days 4 and 5 or epirubicin on day 4, every 21 days. To assess the toxicity and preliminary activity in patients with advanced refractory solid tumors. Patients and Methods: Sixteen patients with progressive dise ase after standard chemotherapy for advanced disease were treated with the combination paclitaxel-ifosfamide and 10 patients with the combination pacl itaxel-epirubicin. Results: In the first phase I study the MTDs were: pacli taxel 135 mg/m(2) and ifosfamide 2.5 mg/m(2)/day; hematologic toxicity was the dose-limiting toxicity (DLT) during the fi rst cycle of therapy at dose level 4. Paclitaxel administered at 135 mg/m(2) and epirubicin 50 mg/m(2) were the MTDs in the second phase I study; grade 4 stomatitis was the DLT o f this combination. Conclusions: Paclitaxel by 72-hour continuous infusion followed by bolus ifosfamide was a manageable regimen with an acceptable he matologic toxicity in the absence of neurotoxicity. Preliminary activity of this combination was encouraging in a group of patients with ovarian cance r. The optimal way to combine paclitaxel and epirubicin and the best schedu le relative to such a long paclitaxel infusion time in this combination reg imen remain to be determined. Copyright (C) 2001 S. Karger AG, Basel.