title: Phase II study of oxaliplatin in children with recurrent or refractory medulloblastoma, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors: a pediatric brain tumor consortium study.
abstract: BACKGROUND
  An open-label Phase II study of oxaliplatin was conducted to evaluate its safety and efficacy in children with recurrent or refractory medulloblastoma (MB), supratentorial primitive neuroectodermal tumors (SPNET), and atypical teratoid rhabdoid tumor (ATRT).
  
  
  METHODS
  Patients were stratified as follows: stratum IA, first recurrence MB with measurable disease; IB, recurrent MB with only cerebral spinal fluid (CSF) positivity or linear leptomeningeal disease (LLD); IC, MB > or =second recurrence; stratum II, recurrent SPNET; stratum III, recurrent ATRT. Patients received oxaliplatin, 130 mg/m(2) intravenously over 2 hours every 3 weeks. The primary objective was to estimate the sustained response rate in stratum 1A. Plasma ultrafiltrate platinum pharmacokinetics were evaluated.
  
  
  RESULTS
  A total of 43 patients with a median age of 8.5 years (range, 0.6-18.9 years) were enrolled. In stratum 1A, 2 of 15 had partial responses (PRs, 1 sustained PR). No responses were observed in other strata. The most frequent Grade 3 and 4 toxicities included thrombocytopenia (25.6%), neutropenia (16.3%), leukopenia (12%), increase in serum alanine transaminase (ALT) (7%), vomiting (4.7%), and sensory neuropathy (4.7%). No severe ototoxicity or nephrotoxicity was reported. Plasma ultrafiltrate platinum pharmacokinetic parameters were similar to adults, with a median clearance of 12.2 L/hr (range, 4.4-30 L/hr) and median area under the curve (AUC(0-infinity)) of 9.4 microg/mL/hr (range, 6.2-13.9 microg/mL/hr).
  
  
  CONCLUSIONS
  Oxaliplatin was well tolerated in children but has limited activity in children with recurrent CNS embryonal tumors previously treated with platinum compounds.
authors.affiliation: St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA. maryam.fouladi@stjude.org
authors.forename: Maryam
authors.initials: M
authors.lastname: Fouladi
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
authors.forename: Tina Young
authors.initials: TY
authors.lastname: Poussaint
authors.forename: Burgess B
authors.initials: BB
authors.lastname: Freeman
authors.forename: Roger
authors.initials: R
authors.lastname: McLendon
authors.forename: Christine
authors.initials: C
authors.lastname: Fuller
authors.forename: Adekunle M
authors.initials: AM
authors.lastname: Adesina
authors.forename: Michael L
authors.initials: ML
authors.lastname: Hancock
authors.forename: Mary K
authors.initials: MK
authors.lastname: Danks
authors.forename: Clinton
authors.initials: C
authors.lastname: Stewart
authors.forename: James M
authors.initials: JM
authors.lastname: Boyett
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077150:Oxaliplatin; D018335:Rhabdoid Tumor / Q000188:drug therapy*; D015173:Supratentorial Neoplasms / Q000188:drug therapy*; D013724:Teratoma / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin