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.
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.
Fouladi
Maryam
M
St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA. maryam.fouladi@stjude.org
Blaney
Susan M
SM
Poussaint
Tina Young
TY
Freeman
Burgess B
BB
McLendon
Roger
R
Fuller
Christine
C
Adesina
Adekunle M
AM
Hancock
Michael L
ML
Danks
Mary K
MK
Stewart
Clinton
C
Boyett
James M
JM
Gajjar
Amar
A
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
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin