title: Carboplatin/ifosfamide window therapy for osteosarcoma: results of the St Jude Children's Research Hospital OS-91 trial.
abstract: OBJECTIVE
  To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin.
  
  
  METHODS
  Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m(2) x 1) and ifosfamide (2.65 g/m(2)/d x 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation.
  
  
  RESULTS
  The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9% v 9%, P: = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3% +/- 6.7% and 76.4% +/- 6.4%, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity.
  
  
  CONCLUSIONS
  This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantial antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.
authors.affiliation: Department of Hematology/Oncology, St Jude Children's Research Hospital, and University of Tennessee Memphis, Memphis, TN, USA. william-meyer@ouhsc.edu
authors.forename: W H
authors.initials: WH
authors.lastname: Meyer
authors.forename: C B
authors.initials: CB
authors.lastname: Pratt
authors.forename: C A
authors.initials: CA
authors.lastname: Poquette
authors.forename: B N
authors.initials: BN
authors.lastname: Rao
authors.forename: D M
authors.initials: DM
authors.lastname: Parham
authors.forename: N M
authors.initials: NM
authors.lastname: Marina
authors.forename: A S
authors.initials: AS
authors.lastname: Pappo
authors.forename: H H
authors.initials: HH
authors.lastname: Mahmoud
authors.forename: J J
authors.initials: JJ
authors.lastname: Jenkins
authors.forename: J
authors.initials: J
authors.lastname: Harper
authors.forename: M
authors.initials: M
authors.lastname: Neel
authors.forename: B D
authors.initials: BD
authors.lastname: Fletcher
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010865:Pilot Projects; D015996:Survival Rate
chemical_list: D016190:Carboplatin; D007069:Ifosfamide