Preradiation chemotherapy in primary high-risk brainstem tumors: phase II study CCG-9941 of the Children's Cancer Group.
OBJECTIVE
This Children's Cancer Group group-wide phase II trial evaluated the efficacy and toxicity of two chemotherapy arms administered before hyperfractionated external-beam radiotherapy (HFEBRT).


METHODS
Thirty-two patients with newly diagnosed brainstem gliomas were randomly assigned to regimen A and 31 to regimen B. Regimen A comprised three courses of carboplatin, etoposide, and vincristine; regimen B comprised cisplatin, etoposide, cyclophosphamide, and vincristine. Both arms included granulocyte colony-stimulating factor. Patients were evaluated by magnetic resonance imaging after induction chemotherapy and HFEBRT at a dose of 72 Gy.


RESULTS
Ten percent +/- 5% of regimen A patients objectively responded to chemotherapy. For combined induction and radiotherapy, 27% +/- 9% of patients improved. The neuroradiographic response rate for regimen B was 19% +/- 8% for chemotherapy and 23% +/- 9% after HFEBRT. Response rates were not statistically significant between regimens after induction or chemotherapy/HFEBRT. Event-free survival was 17% +/- 5% (estimate +/- SE) at 1 year and 6% +/- 3% at 2 years. Survival was significantly longer among patients who responded to chemotherapy (P <.05). Among patients who received regimen A induction, grades 3 and 4 leukopenia were observed in 50% to 65%, with one toxicity-related death. For regimen B, severe leukopenia occurred in 86% to 100%, with febrile neutropenia in 48% to 60% per course.


CONCLUSIONS
Neither chemotherapy regimen meaningfully improved response rate, event-free survival, or overall survival relative to previous series of patients with brainstem gliomas who received radiotherapy with or without chemotherapy.
Jennings
Mark T
MT
Vanderbilt Cancer Center, Nashville, TN, USA. mark.jennings@mcmail.vanderbilt.edu
Sposto
Richard
R
Boyett
James M
JM
Vezina
L Gilbert
LG
Holmes
Emi
E
Berger
Mitchell S
MS
Bruggers
Carol S
CS
Bruner
Janet M
JM
Chan
Ka-Wah
KW
Dusenbery
Kathryn E
KE
Ettinger
Lawrence J
LJ
Fitz
Charles R
CR
Lafond
Deborah
D
Mandelbaum
David E
DE
Massey
Vicky
V
McGuire
Warren
W
McNeely
Lee
L
Moulton
Thomas
T
Pollack
Ian F
IF
Shen
Violet
V
D000293:Adolescent; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D020295:Brain Stem Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage
D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; D002945:Cisplatin