Phase II study of high-dose chemotherapy before radiation in children with newly diagnosed high-grade astrocytoma: final analysis of Children's Cancer Group Study 9933.
BACKGROUND
High-grade astrocytomas (HGA) carry a dismal prognosis and compose nearly 20% of all childhood brain tumors. The role of high-dose chemotherapy (HDCT) in the treatment of HGA remains unclear.


METHODS
In a nationwide study, The Children's Cancer Group (CCG) prospectively evaluated 102 children with HGA and postoperative residual disease for efficacy and toxicity of four courses of HDCT before radiotherapy (RT). Patients were randomly assigned to one of three couplets of drugs: carboplatin/etoposide (Regimen A), ifosfamide/etoposide (Regimen B), or cyclophosphamide/etoposide (Regimen C). After HDCT, all patients were to receive local RT followed by lomustine and vincristine. Twenty-six patients were excluded after central neuroradiographic review (n = 8) or pathology review (n = 18).


RESULTS
Of 76 evaluable patients (median age, 11.95 yrs; range, 3-20 yrs), 30 patients relapsed during HDCT, and 11 others did not complete HDCT because of toxicity. Nonhematologic serious toxicities were common (29%), and 21% of patients did not receive RT. Objective response rates were not associated with amount of residual disease and did not statistically differ between regimens: 27% (Regimen A), 8% (Regimen B), and 29% (Regimen C). Overall survival (OS) was 24% +/- 5% at 5 years and did not differ between groups. Median time to an event was longest for Regimen A (283 days compared with 83 and 91 days for Regimens B and C, respectively). The five-year, event-free survival (EFS) rate for all patients was 8% +/- 3% and 14% +/- 7% for Regimen A (P = 0.07).


CONCLUSIONS
OS and EFS were not affected by histologic grade. Patients who responded to HDCT had a nominally higher survival rate (P = 0.03 for trend). The authors conclude that these commonly used HDCT regimens provide no additional clinical benefit to conventional treatment in HGA, regardless of the amount of measurable residual tumor.
MacDonald
Tobey J
TJ
Department of Hematology-Oncology, Children's National Medical Center, Washington, DC 20010, USA. tmacdona@cnmc.org
Arenson
Edward B
EB
Ater
Joann
J
Sposto
Richard
R
Bevan
Herbert E
HE
Bruner
Janet
J
Deutsch
Melvin
M
Kurczynski
Elizabeth
E
Luerssen
Thomas
T
McGuire-Cullen
Patricia
P
O'Brien
Richard
R
Shah
Narayan
N
Steinbok
Paul
P
Strain
John
J
Thomson
John
J
Holmes
Emi
E
Vezina
Gilbert
G
Yates
Allan
A
Phillips
Peter
P
Packer
Roger
R
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D020295:Brain Stem Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy / Q000379:methods; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D011882:Radiotherapy, High-Energy; D012016:Reference Values; D018570:Risk Assessment; D013120:Spinal Cord Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome