The aim of this phase II study was to evaluate the efficacy and toxicity of two regimens of ifosfamide in metastatic soft tissue sarcoma patients given as first- and second-line chemotherapy. Two different schedules of ifosfamide were investigated in a randomised manner: Ifosfamide was given either at a dose of 5 g/m2 over 24 h (5 g/m2/1 day), every 3 weeks or at a dose of 3 g/m2 per day, administered over 4 h on three consecutive days (3 g/m2/3 days), every 3 weeks. Both schedules were given as first-line or second-line chemotherapy. A total of 182 patients was entered, 103 in first- and 79 in second-line, of whom 8 patients were ineligible, 5 in the first- and 3 in the second-line study. Most patients had a leiomyosarcoma, 46 of the 98 in the first-line and 34 of the 76 in the second-line. The two study arms were well balanced in both the first- and second-lines with respect to sex, age and performance status. In first-line treatment, 5 g/m2/1 day yielded five partial responses (PR) (Response Rate (RR) 10%), versus 12 PR (RR 25%) for the 3 g/m2/3 days. As second-line treatment, the 24-h infusion yielded: one CR and one PR (RR 6%) and the 3-day schedule one CR and two PR (RR 8%). Survival did not differ between the two regimens. The major World Health Organization (WHO) grade 3 and 4 toxicities encountered were: leucopenia in 19% of all courses in the first-line and 32% in the second-line with the 5 g/m2/1 day, while for the 3 g/m2/3 days schedule the rates were 57 and 63% respectively. Grade 3 or 4 infections were seen in 4% of patients treated with 5 g/m2/1 day first-line and 10% of patients given 3 g/m2/3 days, both as first- and second-lines. No such infections were seen in patients receiving 5 g/m2/1 day as second line treatment. In advanced soft-tissue sarcomas in the first-line, ifosfamide 3 g/m2, given over 4 h on three consecutive days, is an active regimen with acceptable toxicity while the 5 g/m2 over 24 hours schedule resulted in a disappointing response rate.

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European Journal of Cancer
Department of Medical Oncology

van Oosterom, A.T, van Glabbeke, M.M.B, Verweij, J, Mouridsen, H.T, Nielsen, O.S, Dombernowsky, P, … Hermans, C. (2002). Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients. European Journal of Cancer, 38(18), 2397–2406. doi:10.1016/S0959-8049(02)00491-4