PHASE-II TRIAL OF FIRST-LINE HIGH-DOSE IFOSFAMIDE IN ADVANCED SOFT-TISSUE SARCOMAS OF THE ADULT - A STUDY OF THE SPANISH GROUP FOR RESEARCHON SARCOMAS (GEIS)

Background: The agent Ifosfamide (IFOS) is active against soft tissue sarcomas (STS), and patients who progress to IFOS at doses less than o r equal to 10 g/m(2) show remissions when exposed to high-dose ifosfam ide (HDI) (i.e., doses > 10 g/m(2)), which supports a dose-response re lationship for this drug. Because of a lack of first-line studies in a dult STS patients, we decided to test the activity and toxicity of HDI in a phase II trial. Patients and methods: Forty-eight patients were enrolled in the study IFOS was administered at a dose of 14 g/m(2) by continuous infusion over six days every four weeks. Granulocyte-macrop hage colony-stimulating factor (GM-CSF) at 5 mu g/kg/day for 10 consec utive days was systematically administered after an episode of neutrop enic fever or a delay in hematologic recovery. Patients were treated u ntil progression or the occurrence of severe toxicity, and surgical re scue was attempted when possible. Results: Six pathology-established c omplete remissions and 11 partial remissions were observed in 45 asses sable patients with a response rate of 37.7% (95% CI: 25.5%-50%). Grad e 3-4 toxicity (% of cycles) was noted by hemoglobin (17%), leukocyte (75%), granulocyte (75%) and platelet (13%) counts in 158 evaluable cy cles. GM-CSF was administered to 28 patients, and 25 suffered one or m ore episodes of neutropenic fever. Renal toxicity was mild and reversi ble with some degree of tubular and glomerular dysfunction detected in up to 60% of patients. Grade 3 CNS toxicity was observed in 32% of pa tients but only one required interruption of therapy. Sixty-four per c ent of the patients had asthenia grade 2-3 and 20% were excluded from the study due to excessive toxicity. There was one treatment-related d eath. Conclusions: HDI is an active drug in first-line therapy against adult STS. Different administration schedules should be evaluated in an attempt to improve its therapeutic index.