Paclitaxel plus ifosfamide in advanced ovarian cancer: results of a phase I study

Patients with advanced ovarian carcinoma and an inadequate response to first-line platinum-based combination chemotherapy (CTX) have a very poor prognosis and effective salvage regimens are clearly needed. This phase I study was performed in order to determine the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of the combination paclitaxel (P) and ifosfamide (IFO). After premedication, patients received P as a 3 h i.v. infusion on day 1; IFO was given as 1 h i.v. infusion with the standard dose of mesna i.v. on days 2-5, q day 22. The following dose levels (dl) were investigated: (mg/m(2)/day) dI1, P 135/IFO 1500; dI2, P 135/IFO 2000; dI3, P 175/IFO 2000; and dI4, P 175/IFO 1500. Eighteen patients with advanced ovarian cancer entered this trial. In eight patients treated with an IFO dose of 2000 mg/m(2) during dI2 and 3, two required treatment interruptions because of CNS toxicity CTC grade 3 and one patient experienced nephrotoxicity CTC grade 3, Therefore the MTD of IFO used in combination with P and given over 4 days is reached with 2000 mg/m(2) /day. In the fourth dI we escalated the P dose up to 175 mg/m(2), reduced the IFO dose to 1500 mg/m(2) and treated an additonal five patients. No DLT occured at that dl. Objective responses were observed at all dIs. The combination of P and IFO is feasable and active in pretreated advanced ovarian carcinoma. dI4 is the recommended dose for phase II trials. [(C) 1998 Lippincott-Raven Publishers.].