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

Aims and background: 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/m ² iv and the dose increase was 1 g/m ² every four weeks for a total of five courses; 12 g/m ² 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/m ² ifosfamide, 3 11 g/m ² and 3 12 g/m ². 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. Conclusion: 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.