title: Long-term results of a multicenter SAKK trial on high-dose ifosfamide and doxorubicin in advanced or metastatic gynecologic sarcomas.
abstract: BACKGROUND
  Dose intensive chemotherapy has not been tested prospectively for the treatment of gynecologic sarcomas. We investigated the antitumor activity and toxicity of high-dose ifosfamide and doxorubicin, in the context of a multidisciplinary strategy for the treatment of advanced and metastatic, not pretreated, gynecologic sarcomas.
  
  
  METHODS
  Thirty-nine patients were enrolled onto a phase I-II multicenter trial of ifosfamide, 10 g/m2 as a continuous infusion over 5 days, plus doxorubicin intravenously, 25 mg/m2/day for 3 days with Mesna and granulocyte-colony-stimulating factor every 21 days. Salvage therapy was allowed after chemotherapy.
  
  
  RESULTS
  Among the 37 evaluable patients, the tumor was locally advanced (n = 11), with concomitant distant metastases (n = 5) or with distant metastases only (n = 21). After a median of three (range 1-7) chemotherapy cycles, six patients experienced a complete response and 12 a partial response for an overall response rate of 49% (95% CI 32% to 66%). The response rate was higher in poorly differentiated tumors (62%) compared with moderately well differentiated ones (18%), but was not different according to histology subtypes. Eleven patients had salvage therapy, either immediately following chemotherapy (n = 7) or at time of progression (n = 4). With a median follow-up time of 5 years, the median overall survival was 30.5 months. Hematological toxicity was as expected neutropenia, thrombopenia and anemia > or = grade 3 at 50%, 34% and 33% of cycles respectively. No toxic death occurred.
  
  
  CONCLUSIONS
  High-dose ifosfamide plus doxorubicin is an active regimen for all subtypes of gynecological sarcomas. Its toxicity was manageable in a multicentric setting. The prolonged survival might be due to the multidisciplinary strategy that was possible in one-third of the patients.
authors.affiliation: Centre Pluridisciplinaire d'Oncologie, University Hospital, Lausanne, Switzerland. Serge.Leyvraz@hospvd.ch
authors.forename: S
authors.initials: S
authors.lastname: Leyvraz
authors.forename: M
authors.initials: M
authors.lastname: Zweifel
authors.forename: G
authors.initials: G
authors.lastname: Jundt
authors.forename: A
authors.initials: A
authors.lastname: Lissoni
authors.forename: T
authors.initials: T
authors.lastname: Cerny
authors.forename: C
authors.initials: C
authors.lastname: Sessa
authors.forename: M
authors.initials: M
authors.lastname: Fey
authors.forename: D
authors.initials: D
authors.lastname: Dietrich
authors.forename: H P
authors.initials: HP
authors.lastname: Honegger
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis
chemical_list: D004317:Doxorubicin; D007069:Ifosfamide