A phase I-II trial of high-dose ifosfamide in patients with ovarian cancer refractory or resistant to platinum and/or paclitaxel-containing chemotherapy.
OBJECTIVE
To evaluate the toxicity of high-dose ifosfamide in ovarian cancer patients refractory or resistant to platinum and/or paclitaxel-containing chemotherapy.


METHODS
This was an open, non-randomized phase I-II trial of high-dose ifosfamide. Eligibility criteria were: patients aged 18-75 years affected by ovarian cancer with refractory or resistant disease or early relapse after first-line treatment including platinum or paclitaxel. Three patients were given escalating ifosfamide doses; if no severe adverse events occurred, the ifosfamide dose was increased. The starting dose of ifosfamide was 10 g/m2 i.v. and the dose increase was 1 g/m2 every four weeks for a total of five courses; 12 g/m2 was the maximum ifosfamide dose to be administered. The trial then progressed to a phase II trial, in which ifosfamide was given at the maximum tolerated dose reached during the escalating dose phase.


RESULTS
A total of 36 patients entered the trial. Nine patients were involved in phase I of the study; 3 received 10 g/m2 ifosfamide, 3 11 g/m2 and 3 12 g/m2. Of the 32 evaluable patients 6 (18.8%) achieved a complete response and three (9.4%) a partial response, giving an overall response rate of 28.1% (95% CI, 15-61% based on Poisson's approximation). The median number of ifosfamide courses was five. G1, G2 and G3 neurotoxicity was reported in 3 (8%), 2 (5%) and 2 (5%) patients, respectively.


CONCLUSIONS
This phase I-II trial indicates that high-dose ifosfamide has some activity but also a relevant degree of toxicity in resistant or refractory platinum and paclitaxel-pretreated ovarian cancer.
Scarfone
G
G
Prima Clinica Ostetrico-Ginecologica, Università di Milano, Milan, Italy.
Villa
A
A
Parazzini
F
F
Sciatta
C
C
Polverino
G
G
Bolis
G
G
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000494:pharmacology; D017671:Platinum Compounds / Q000494:pharmacology; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D017671:Platinum Compounds; D017239:Paclitaxel; D007069:Ifosfamide