title: Treatment of metastatic osteosarcoma at diagnosis: a Pediatric Oncology Group Study.
abstract: OBJECTIVE
  To estimate the duration of survival (S) of patients with metastatic osteosarcoma (MOS) at diagnosis treated with a multiagent, ifosfamide-containing chemotherapeutic and surgical regimen and to evaluate the toxicity of this regimen.
  
  
  METHODS
  Thirty patients aged younger than 30 years received two courses of ifosfamide followed by surgery on the primary tumor and metastatic sites. Patients then received a postsurgical multiagent chemotherapeutic regimen that consisted of high-dose methotrexate (HDMTX), ifosfamide, doxorubicin, and cisplatin.
  
  
  RESULTS
  The 5-year event-free survival (EFS) rate was 46.7% (95% confidence interval [CI]; 28.5 to 64.9) and 5-year S rate was 53.3% (95% CI; 35.1 to 71.5). Three patients with bone metastases and one patient with lymph node metastases died. Twenty-six patients presented with pulmonary metastatic nodules only. Eight of these patients had at least eight nodules at diagnosis and had an estimated 5-year EFS rate of 25.0% compared with 66.7% for the 18 patients with less than eight nodules (P=.06). Fourteen patients presented with bilateral lung metastases and had a 5-year EFS rate of 35.7% compared with the 12 patients who presented with unilateral involvement and had a 5-year EFS rate of 75.0% (P=.03). The hematopoietic toxicity experienced by the patients during the entire regimen was relatively mild. Seven patients had renal toxicity characterized by hypophosphatemia and/or hypokalemia.
  
  
  CONCLUSIONS
  This ifosfamide-containing regimen is tolerable and effective in the treatment of patients with osteosarcoma (OS) who present with lung metastases. However, better regimens are required for this group of patients.
authors.affiliation: Tomorrow's Children's Institute, Hackensack University Medical Center, NJ, USA. wendyb@nwu.edu
authors.forename: M B
authors.initials: MB
authors.lastname: Harris
authors.forename: P
authors.initials: P
authors.lastname: Gieser
authors.forename: A M
authors.initials: AM
authors.lastname: Goorin
authors.forename: A
authors.initials: A
authors.lastname: Ayala
authors.forename: S J
authors.initials: SJ
authors.lastname: Shochat
authors.forename: W S
authors.initials: WS
authors.lastname: Ferguson
authors.forename: T
authors.initials: T
authors.lastname: Holbrook
authors.forename: M P
authors.initials: MP
authors.lastname: Link
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D012516:Osteosarcoma / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D013997:Time Factors
chemical_list: D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate