title: Benefit from prolonged dose-intensive chemotherapy for infants with malignant brain tumors is restricted to patients with ependymoma: a report of the Pediatric Oncology Group randomized controlled trial 9233/34.
abstract: BACKGROUND
  The randomized controlled Pediatric Oncology Group study 9233 tested the hypothesis that dose-intensive (DI) chemotherapy would improve event-free survival (EFS) for children <3 years of age with newly diagnosed malignant brain tumors.
  
  
  METHODS
  Of 328 enrolled eligible patients, diagnoses were medulloblastoma (n = 112), ependymoma (n = 82), supratentorial primitive neuroectodermal tumor (sPNET, n = 38) and other malignant brain tumors (n = 96), and were randomized to 72 weeks of standard dose chemotherapy (Regimen A, n = 162) or DI chemotherapy (Regimen B, n = 166). Radiation therapy (RT) was recommended for patients with evidence of disease at completion of chemotherapy or who relapsed within 6 months of chemotherapy completion.
  
  
  RESULTS
  Distributions of EFS for Regimens A and B were not significantly different (P = 0.32) with 2- and 10-year rates of 22.8% ± 3.3% and 15.4% ± 3.7%, and 27.1% ± 3.4% and 20.8% ± 3.8%, respectively. Thus, the study hypothesis was rejected. While distributions of EFS and OS were not significantly different between Regimens A and B for patients with medulloblastoma and sPNET, DI chemotherapy resulted in significantly improved EFS distribution (P = .0011) (2-year EFS rates of 42.1% vs. 19.6% with SD chemotherapy), but not OS distribution, for patients with centrally confirmed ependymoma. The degree of surgical resection affected EFS, OS or both for most tumor groups. Approximately 20%, 40% and 20% of patients with medulloblastoma, ependymoma treated with DI chemotherapy, and sPNET, respectively appear to have been cured without RT. Of 11 toxic deaths on study, 10 occurred on the DI chemotherapy arm.
  
  
  CONCLUSIONS
  Prolonged dose-intensive chemotherapy given to infants with malignant brain tumors resulted in increased EFS only for patients with ependymoma.
authors: University of Calgary, Calgary, Canada (D.R.S., L.L.-C.); St Jude Children's Research Hospital, Memphis, Tennessee (J.M.B., L.E.K., A.G.); Johns Hopkins University, Baltimore, Maryland (P.B.); Dell Children's Medical Center of Central Texas, Austin, Texas (P.A.); University of Rochester, Rochester, New York (L.C.); (retired) Roswell Park Cancer Institute, Buffalo, New York (P.D.); University of Tennessee Health Science Center, Tennessee (M.K.); Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas (M.E.H.).
authors: Douglas R
authors: DR
authors: Strother
authors: Lucie
authors: L
authors: Lafay-Cousin
authors: James M
authors: JM
authors: Boyett
authors: Peter
authors: P
authors: Burger
authors: Patricia
authors: P
authors: Aronin
authors: Louis
authors: L
authors: Constine
authors: Patricia
authors: P
authors: Duffner
authors: Mehmet
authors: M
authors: Kocak
authors: Larry E
authors: LE
authors: Kun
authors: Marc E
authors: ME
authors: Horowitz
authors: Amar
authors: A
authors: Gajjar
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002675:Child, Preschool; D004806:Ependymoma / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy; D015173:Supratentorial Neoplasms / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: brain tumors; chemotherapy; dose-intensive; infants