title: Phase II trial of ifosfamide and cisplatin in the treatment of metastatic sarcomas: a Southwest Oncology Group study.
abstract: The Southwest Oncology Group (SWOG) performed a phase II trial of a combination of ifosfamide/mesna/cisplatin in patients with metastatic soft-tissue sarcoma who had previously received one chemotherapeutic regimen. A total of 39 patients were registered in the study, including 7 treated during a limited-institution pilot phase; 38 patients were fully eligible and evaluable. During the pilot phase, patients were treated with 2.5 g/m2 ifosfamide daily on days 1-3, 2.5 g/m2 mesna daily on days 1-4, and 100 mg/m2 cisplatin on days 2 and 9. Due to excessive myelosuppression, the day-9 cisplatin dose was dropped when the study was opened groupwide, and the subsequent 32 patients were treated at 3- to 4-week intervals with 2.5 g/m2 ifosfamide daily on days 1-3, 2.5 g/m2 mesna daily on days 1-4, and 100 mg/m2 cisplatin on day 2. Myelosuppression was severe, with granulocytopenia (< 0.5 x 10(9)/l) being observed in 26 of 38 patients. Three cases of National Cancer Institute grade 3 or 4 nephrotoxicity (serum creatinine, > 3 times the normal value) and three cases of grade 3 or 4 central nervous system toxicity were reported. Overall, three complete and five partial responses were achieved, for a major response rate of 21%. The median survival of all patients was 11 months. We conclude that ifosfamide-based chemotherapy can produce objective responses in previously treated patients with metastatic soft-tissue sarcoma but that cisplatin increases the toxicity of therapy. Phase II trials of new agents are needed to identify drugs with clinical activity in the treatment of soft-tissue sarcomas.
authors.affiliation: Department of Hematology/Medical Oncology, Cleveland Clinic Foundation, Ohio.
authors.forename: G T
authors.initials: GT
authors.lastname: Budd
authors.forename: B
authors.initials: B
authors.lastname: Metch
authors.forename: S A
authors.initials: SA
authors.lastname: Weiss
authors.forename: J K
authors.initials: JK
authors.lastname: Weick
authors.forename: C
authors.initials: C
authors.lastname: Fabian
authors.forename: R L
authors.initials: RL
authors.lastname: Stephens
authors.forename: S P
authors.initials: SP
authors.lastname: Balcerzak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis
chemical_list: D002945:Cisplatin; D007069:Ifosfamide