Phase I trial of ifosfamide and 24-h infusional paclitaxel in pelvic malignancies: A Gynecologic Oncology Group study

Objective. The goal of this work was to develop a combination chemotherapy regimen consisting of ifosfamide and paclitaxel to be evaluated in the mana gement of gynecologic malignancies, Methods, The Gynecologic Oncology Group conducted a Phase I trial of the re gimen, initially with paclitaxel (24-h infusion) delivered on Day 1 and ifo sfamide (1 h) administered (with Mesna) over the subsequent 4 days. All pat ients received granulocyte colony-stimulating factor (G-CSF) starling 24 h after the Day 5 chemotherapy. Treatment was repeated on a 28-day schedule. A cohort of patients also received the alternate sequence of ifosfamide (4 days) followed by paclitaxel. Results, Twenty-two patients were evaluated, Even at the lowest dose level tested (paclitaxel 135 mg/m(2) followed by ifosfamide 1 g/m(2)/day x 4 days ) grade 4 neutropenia was almost universal, despite the routine use of G-CS F, The alternate drug administration sequence resulted in marrow suppressio n of similar severity. Conclusion. The combination of 24-h infusional paclitaxel with ifosfamide d elivered over 4 days results in severe neutropenia, despite the administrat ion of G-CSF, and is not recommended for further evaluation. In view of the known activity of the two agents in several malignancies, including cervix cancer, it would be reasonable to investigate the delivery of the agents e mploying alternative treatment schedules predicted to result in less severe marrow suppression (e.g., 3-h infusional paclitaxel), (C) 2001 Academic Pr ess.