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 disease after standard chemotherapy for advanced disease were treated with the combination paclitaxel-ifosfamide and 10 patients with the combination paclitaxel-epirubicin. RESULTS: In the first phase I study the MTDs were: paclitaxel 135 mg/m2 and ifosfamide 2.5 mg/m2/day; hematologic toxicity was the dose-limiting toxicity (DLT) during the first cycle of therapy at dose level 4. Paclitaxel administered at 135 mg/m2 and epirubicin 50 mg/m2 were the MTDs in the second phase I study; grade 4 stomatitis was the DLT of this combination. CONCLUSIONS: Paclitaxel by 72-hour continuous infusion followed by bolus ifosfamide was a manageable regimen with an acceptable hematologic toxicity in the absence of neurotoxicity. Preliminary activity of this combination was encouraging in a group of patients with ovarian cancer. The optimal way to combine paclitaxel and epirubicin and the best schedule relative to such a long paclitaxel infusion time in this combination regimen remain to be determined.