title: Treatment of children with poor risk solid tumors by further escalation of the VETOPEC regimen including very high-dose cyclophosphamide and peripheral stem cell support: an Australian and New Zealand Children's Hematology and Oncology Group study.
abstract: BACKGROUND
  Children with solid tumors deemed to be poor risk at diagnosis and those who fail to respond or recur after chemotherapy have adverse outcomes. We sought to increase the dosage of cyclophosphamide (CPA) in the VETOPEC regimen (vincristine, etoposide, and CPA) with a view to improving the response rate and survival.
  
  
  METHODS
  Patients underwent peripheral blood stem cell (PBSC) harvest after standard dose VETOPEC (CPA 40 mg/kg/day for 3 days) followed by filgrastim. Those with sufficient PBSC received up to four intensive cycles (ICs) of VETOPEC with CPA dosages of 60-90 mg/kg/day for 3 days (escalated by 5 mg/kg/day in cohorts of at least five patients) followed by PBSC and filgrastim.
  
  
  RESULTS
  Of the 59 enrolled patients, 58 were treated with mobilization chemotherapy and 57 proceeded to PBSC harvest. From 1 to 4 VETOPEC ICs were administered to 51 patients. The maximum tolerated dosage of CPA was not reached. The best response rate during the ICs for patients with recurrent or refractory/progressive disease was 67%; overall survival was 28% at 5 years and 25% at 10 years. The response rate for patients with newly diagnosed high-risk tumors was 89%.
  
  
  CONCLUSIONS
  The VETOPEC regimen with CPA dosages up to 90 mg/kg/day for 3 days followed by PBSC and filgrastim can be given in a timely manner with manageable toxicity. Outcomes were not improved when compared to prior VETOPEC studies. VETOPEC produces high response rates and warrants further evaluation in appropriate patients with newly diagnosed high-risk solid tumors.
authors.affiliation: Oncology Unit, The Children's Hospital at Westmead, Sydney, NSW, Australia. geoffm@chw.edu.au
authors.forename: Geoffrey B
authors.initials: GB
authors.lastname: McCowage
authors.forename: Robert
authors.initials: R
authors.lastname: Mrongovius
authors.forename: Frank
authors.initials: F
authors.lastname: Alvaro
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cohn
authors.forename: David S
authors.initials: DS
authors.lastname: Ziegler
authors.forename: Cecilia
authors.initials: C
authors.lastname: Oswald
authors.forename: Les
authors.initials: L
authors.lastname: White
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001315:Australia; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000628:therapy*; D009520:New Zealand; D036102:Peripheral Blood Stem Cell Transplantation; D012307:Risk Factors; D016019:Survival Analysis; D014182:Transplantation, Autologous; D055815:Young Adult
chemical_list: D003520:Cyclophosphamide