Effect of high-dose ifosfamide in advanced soft tissue sarcomas. A multicentre phase II study of the EORTC Soft Tissue and Bone Sarcoma Group

In this phase II study the effect of high-dose ifosfamide (HDI) given as a 3-day continuous infusion at a dose of 12 g/m(2) repeated every 4 weeks wit h adequate mesna protection and hydration was evaluated in patients with ad vanced soft tissue sarcomas. A total of 124 patients entered the trial of w hich 10 were ineligible. HDI was given both as first-line and second-line c hemotherapy. Median age was 46 years (19-66 years). Median World Health Org anization (WHO) performance status was 1 (0-1). Fifty two per cent of the p atients were males. The predominant histology was leiomyosarcoma (33%). A m aximum of six cycles was given. At the time of analysis 55 patients have di ed. The partial response (PR) rate was 16%. The median time to progression was 15 weeks. 8 of the 18 responding: patients (44%) had synovial sarcomas, whereas only 5% of the patients having leiomyosarcomas responded. The grad e 3 + 4 haematological toxicity encountered was neutrophils in 78% and plat elets in 12%. The major grade 3 + 4 non-haematological toxicities encounter ed were febrile neutropenia in 39%, infection in 20%, and acute renal failu re in 4%. In conclusion, it is possible to administer HDI on a multicentre basis, but the toxicity is substantial. HDI given as a continuous infusion at this dose cannot be recommended as the standard treatment of advanced so ft tissue sarcomas, even in selected patients. (C) 2000 Elsevier Science Lt d. All rights reserved.