Carboplatin and etoposide with hyperfractionated radiotherapy in children with newly diagnosed diffuse pontine gliomas: a phase I/II study.
BACKGROUND
Diffuse pontine gliomas remain one of the most lethal of pediatric malignancies despite the use of increasingly intensive therapies. We delivered intensive chemotherapy during and following 70.2 Gy of hyperfractionated radiation therapy in an attempt to improve survival.


METHODS
Nine consecutive children with diffuse pontine gliomas were treated on this single arm study. Carboplatin, given in combination with fixed dose etoposide, was escalated in successive cohorts to determine its maximum tolerated systemic exposure (AUC). Outcome was coded based on imaging characteristics and clinical status.


RESULTS
Eight of the nine children on this study died of their disease at a median of 44 weeks, essentially the same survival as those treated on a previous Pediatric Oncology Group study using hyperfractionated radiation therapy alone. Toxicity was almost exclusively hematologic and not associated with significant morbidity.


CONCLUSIONS
The use of concurrent carboplatin and etoposide with hyperfractionated radiation therapy did not appear to improve the survival in this group of children with diffuse pontine gliomas. The toxicity of this chemotherapy during radiation therapy was primarily hematologic and well tolerated. New approaches to the treatment of these tumors need to be investigated.
Walter
A W
AW
Department of Hematology-Oncology, St. Jude Children's Research Hospital, University of Tennessee, Memphis 38105, USA.
Gajjar
A
A
Ochs
J S
JS
Langston
J W
JW
Sanford
R A
RA
Kun
L E
LE
Heideman
R
R
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D011149:Pons; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D016190:Carboplatin