title: High-dose chemotherapy consolidation for chemosensitive advanced soft tissue sarcoma patients: an open-label, randomized controlled trial.
abstract: BACKGROUND
  Metastatic soft tissue sarcoma (STS) prognosis remains poor and few cytotoxic agents offer proven efficacy. This randomized open phase III study examines whether high-dose (HD) chemotherapy with peripheral blood stem cells (PBSCs) could improve overall survival (OS) of chemosensitive patients.
  
  
  METHODS
  Advanced STS patients aged 18-65 years received four courses of standard mesna, adryamycin, ifosfamide and dacarbazine (MAID) treatment. Chemotherapy-responding patients and patients with at least stable disease amenable to complete surgical resection were randomized to receive standard dose (SD) with two successive MAID cycles or HD treatments of one MAID then MICE intensification: mesna (3.6 g/m(2), day 1-5), ifosfamide (2.5 g/m(2), day 1-4), carboplatin [area under the curve (AUC) 5/day 2-4] and etoposide (300 mg/m(2), day 1-4) with PBSC reinjection at day 7.
  
  
  RESULTS
  From 2000 to 2008, 207 patients received four cycles of MAID and 87 assessable patients were randomly assigned to receive the following: 46 SD, 41 HD, with 45 and 38 maintained for analyses after secondary centralized histological review. Futility analyses led to study closure in November 2008. Three-year OS was 49.4% for the SD group versus 32.7% for HD arm, hazard ratio= 1.26, 95% confidence interval 0.70-2.29; progression-free survival was 32.4% and 14.0%, respectively. HD treatment led to higher grades 3-4 toxicity.
  
  
  CONCLUSIONS
  This study failed to show an OS advantage for advanced STS patients treated with dose-intensified chemotherapy with PBSC.
authors.affiliation: Department of Medical Oncology, Institut Bergonié, Bordeaux. Electronic address: bui@bergonie.org.
authors.forename: B
authors.initials: B
authors.lastname: Bui-Nguyen
authors.affiliation: Center Léon Bérard, Lyon.
authors.forename: I
authors.initials: I
authors.lastname: Ray-Coquard
authors.affiliation: Institut Claudius Regaud, Toulouse.
authors.forename: C
authors.initials: C
authors.lastname: Chevreau
authors.affiliation: Center Oscar Lambret, Lille.
authors.forename: N
authors.initials: N
authors.lastname: Penel
authors.affiliation: Center Jean Perrin, Center Hospitalier Universitaire Estaing, Clermont-Ferrand.
authors.forename: J O
authors.initials: JO
authors.lastname: Bay
authors.affiliation: Department of Pathology and INSERM U916, Institut Bergonié, Bordeaux.
authors.forename: J M
authors.initials: JM
authors.lastname: Coindre
authors.affiliation: Center Val d'Aurelle-Paul Lamarque, Montpellier.
authors.forename: D
authors.initials: D
authors.lastname: Cupissol
authors.affiliation: Department of Medical Oncology, Institut Bergonié, Bordeaux.
authors.forename: A
authors.initials: A
authors.lastname: Italiano
authors.affiliation: Clinical and Epidemiological Research Unit, Institut Bergonié and Inserm CIC-EC 7, Bordeaux.
authors.forename: F
authors.initials: F
authors.lastname: Bonichon
authors.affiliation: Hôpital Tenon, Paris.
authors.forename: J P
authors.initials: JP
authors.lastname: Lotz
authors.affiliation: Center Antoine-Lacassagne, Nice.
authors.forename: A
authors.initials: A
authors.lastname: Thyss
authors.affiliation: French National Federation for Comprehensive Cancer Centers, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Jimenez
authors.affiliation: Clinical and Epidemiological Research Unit, Institut Bergonié and Inserm CIC-EC 7, Bordeaux.
authors.forename: S
authors.initials: S
authors.lastname: Mathoulin-Pélissier
authors.affiliation: Center Léon Bérard, Lyon.
authors.forename: J Y
authors.initials: JY
authors.lastname: Blay
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D060830:Consolidation Chemotherapy / Q000379:methods*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008297:Male; D015080:Mesna / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D012509:Sarcoma / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D005047:Etoposide; D003606:Dacarbazine; D004317:Doxorubicin; D016190:Carboplatin; D015080:Mesna; D007069:Ifosfamide