title: Adjuvant therapy of osteosarcoma--A Phase II trial: Southwest Oncology Group study 9139.
abstract: BACKGROUND
  The objective of this study was to estimate the time to treatment failure and survival rate of the three-drug combination of doxorubicin, cisplatin, and ifosfamide as primary and postoperative, adjunctive treatment for teenagers and adults with osteosarcoma (OS).
  
  
  METHODS
  Sixty-three eligible patients with nonmetastatic OS of the extremities were registered from 24 institutions from February, 1992 through December, 1996. Chemotherapy was comprised of doxorubicin at a dose of 75 mg/m2 and cisplatin at a dose of 120 mg/m2, alternating with doxorubicin at a dose of 50 mg/m2 and ifosfamide at a dose of 8 g/m2. Four cycles were given prior to surgical resection, and four cycles were given after surgery. Outcome measures included the time to treatment failure, overall survival, toxicity, and centralized assessment of tumor necrosis.
  
  
  RESULTS
  Thirty-one of 63 eligible patients died, for a 5-year overall survival rate of 58% (95% confidence interval [95% CI], 46-71%). The median time to treatment failure was 19 months (95% CI, 12-41 months). A good pathologic response (> or = 90% necrosis) to neoadjuvant chemotherapy was observed in 48% of patients who underwent surgery. There was no correlation noted between response to neoadjuvant chemotherapy and patient outcome. Grade 4 hematologic toxicities were frequent (89%), although serious nonhematologic toxicities other than nausea and emesis were uncommon.
  
  
  CONCLUSIONS
  The regimen and schedule used in the current study did not improve outcomes compared with prior trials of doxorubicin and cisplatin alone. New, more effective drugs are needed for the treatment of patients with OS. The identification and utilization of molecular markers to predict outcome and response to therapy would facilitate clinical management, limiting exposure to toxic therapies for patients with favorable molecular profiles and identifying those patients who may fail with current approaches as candidates for clinical trials.
authors.affiliation: Department of Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Zalupski
authors.forename: Cathryn
authors.initials: C
authors.lastname: Rankin
authors.forename: James R
authors.initials: JR
authors.lastname: Ryan
authors.forename: David R
authors.initials: DR
authors.lastname: Lucas
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Muler
authors.forename: Keith S
authors.initials: KS
authors.lastname: Lanier
authors.forename: George Thomas
authors.initials: GT
authors.lastname: Budd
authors.forename: J Sybil
authors.initials: JS
authors.lastname: Biermann
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Meyers
authors.forename: Karen
authors.initials: K
authors.lastname: Antman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide