title: 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.
abstract: 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/m(2) over 24 h (5 g/m(2)/1 day), every 3 weeks or at a dose of 3 g/m(2) per day, administered over 4 h on three consecutive days (3 g/m(2)/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/m(2)/1 day yielded five partial responses (PR) (Response Rate (RR) 10%), versus 12 PR (RR 25%) for the 3 g/m(2)/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/m(2)/1 day, while for the 3 g/m(2)/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/m(2)/1 day first-line and 10% of patients given 3 g/m(2)/3 days, both as first- and second-lines. No such infections were seen in patients receiving 5 g/m(2)/1 day as second line treatment. In advanced soft-tissue sarcomas in the first-line, ifosfamide 3 g/m(2), given over 4 h on three consecutive days, is an active regimen with acceptable toxicity while the 5 g/m(2) over 24 hours schedule resulted in a disappointing response rate.
authors.affiliation: Department of Oncology, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium. allan.vanoosterom@uz.kuleuven.ac.be
authors.forename: A T
authors.initials: AT
authors.lastname: van Oosterom
authors.forename: H T
authors.initials: HT
authors.lastname: Mouridsen
authors.forename: O S
authors.initials: OS
authors.lastname: Nielsen
authors.forename: P
authors.initials: P
authors.lastname: Dombernowsky
authors.forename: K
authors.initials: K
authors.lastname: Krzemieniecki
authors.forename: I
authors.initials: I
authors.lastname: Judson
authors.forename: L
authors.initials: L
authors.lastname: Svancarova
authors.forename: D
authors.initials: D
authors.lastname: Spooner
authors.forename: C
authors.initials: C
authors.lastname: Hermans
authors.forename: M
authors.initials: M
authors.lastname: Van Glabbeke
authors.forename: J
authors.initials: J
authors.lastname: Verweij
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000627:therapeutic use*; D007890:Leiomyosarcoma / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012509:Sarcoma / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007069:Ifosfamide