title: Paclitaxel plus ifosfamide in advanced ovarian cancer: results of a phase I study.
abstract: 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/m2/day) dl1, P 135/IFO 1500; dl2, P 135/IFO 2000; dl3, P 175/IFO 2000; and dl4, P 175/ IFO 1500. Eighteen patients with advanced ovarian cancer entered this trial. In eight patients treated with an IFO dose of 2000 mg/m2 during dl2 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/m2/day. In the fourth dl we escalated the P dose up to 175 mg/m2, reduced the IFO dose to 1500 mg/m2 and treated an additional five patients. No DLT occurred at that dl. Objective responses were observed at all dls. The combination of P and IFO is feasible and active in pretreated advanced ovarian carcinoma. dl4 is the recommended dose for phase II trials.
authors.affiliation: Department of Internal Medicine (Cancer Research), West German Cancer Center, University of Essen.
authors.forename: U
authors.initials: U
authors.lastname: Klaassen
authors.forename: A
authors.initials: A
authors.lastname: Harstrick
authors.forename: D
authors.initials: D
authors.lastname: Strumberg
authors.forename: H
authors.initials: H
authors.lastname: Wilke
authors.forename: S
authors.initials: S
authors.lastname: Seeber
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002927:Cimetidine / Q000627:therapeutic use; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects*; D011292:Premedication
chemical_list: D003907:Dexamethasone; D002927:Cimetidine; D017239:Paclitaxel; D007069:Ifosfamide