title: Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial.
abstract: OBJECTIVE
  The objectives of this trial were to estimate the response rate, progression-free survival, and overall survival of patients who received therapy with etoposide and high-dose ifosfamide, and to define the toxicity of this combination when provided with standard chemotherapy in patients with newly diagnosed metastatic osteosarcoma.
  
  
  METHODS
  Eligible patients received infusions of 100 mg/m(2) per day of etoposide and 3.5 g/m(2) per day of ifosfamide for 5 days. Therapy with granulocyte colony-stimulating factor was begun on day 6. This was repeated 3 weeks after therapy was begun. Response was determined at week 6 by both standard World Health Organization response criteria and by pathologic determination of tumor necrosis of the primary tumor.
  
  
  RESULTS
  Forty-three patients were registered; 39 were assessable for response and 41 for toxicity and survival. Twenty-eight (68%) of 41 had metastatic sites only in the lung; 12 (29%) had metastatic sites in other bones with or without lung involvement. Four patients (10%) experienced complete response, and 19 patients (49%) experienced partial response, for an overall response rate of 59% +/- 8%. The projected 2-year progression-free survival (PFS) for the 28 patients with metastases to lungs was 39% +/- 11%. The projected 2-year PFS for the 12 patients with metastases to other bones (with or without pulmonary metastases) was 58% +/- 17%. Two patients died as a result of therapy toxicity. Eighty-three percent of patients had grade 4 neutropenia, and 29% had grade 4 thrombocytopenia. Ten patients (24%) had sepsis. Fanconi's syndrome was observed in five patients.
  
  
  CONCLUSIONS
  The combination of etoposide and high-dose ifosfamide is effective induction chemotherapy for patients with metastatic osteosarcoma, despite significant associated myelosuppression sometimes complicated by infection and renal toxicity.
authors.affiliation: Dana-Farber Cancer Institute, The Children's Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. allen_goorin@dfci.harvard.edu
authors.forename: Allen M
authors.initials: AM
authors.lastname: Goorin
authors.forename: Michael B
authors.initials: MB
authors.lastname: Harris
authors.forename: Mark
authors.initials: M
authors.lastname: Bernstein
authors.forename: William
authors.initials: W
authors.lastname: Ferguson
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Gene P
authors.initials: GP
authors.lastname: Siegal
authors.forename: Mark C
authors.initials: MC
authors.lastname: Gebhardt
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Schwartz
authors.forename: Michael
authors.initials: M
authors.lastname: Link
authors.forename: Holcombe E
authors.initials: HE
authors.lastname: Grier
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002648:Child; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007262:Infusions, Intravenous; D008297:Male; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D007069:Ifosfamide