A phase II study of preradiotherapy chemotherapy followed by hyperfractionated radiotherapy for newly diagnosed high-risk medulloblastoma/primitive neuroectodermal tumor: a report from the Children's Oncology Group (CCG 9931).
OBJECTIVE
To verify feasibility and monitor progression-free survival and overall survival in children with high-risk medulloblastoma and noncerebellar primitive neuroectodermal tumors (PNETs) treated in a Phase II study with preradiotherapy chemotherapy (CHT) followed by high-dose, hyperfractionated craniospinal radiotherapy (CSRT).


METHODS
Eligibility criteria included age >3 years at diagnosis, medulloblastoma with either high M stage and/or >1.5 cm(2) postoperative residual disease, and all patients with noncerebellar PNET. Treatment was initiated with five alternating monthly cycles of CHT (A [cisplatin, cyclophosphamide, etoposide, and vincristine], B [carboplatin and etoposide], A, B, and A) followed by hyperfractionated CSRT (40 Gy) with a boost to the primary tumor (72 Gy) given in twice-daily 1-Gy fractions.


RESULTS
The valid study group consisted of 124 patients whose median age at diagnosis was 7.8 years. Eighty-four patients (68%) completed the entire protocol according to study guidelines (within 9 months), and the median time to complete CSRT was 1.6 months. Major reasons for failure to complete CHT included progressive disease (17%) and toxic death (2.4%). The 5-year progression-free survival and overall survival rates were 43% +/- 5% and 52% +/- 5%, respectively. No significant differences were detected in subset analysis related to response to CHT, site of primary tumor, postoperative residual disease, or M stage.


CONCLUSIONS
The feasibility of this intensive multimodality protocol was confirmed, and response to pre-RT CHT did not impact on survival. Survival data from this protocol can not be compared with data from other studies, given the protocol design.
Allen
Jeffrey
J
Departments of Pediatrics and Pathology, New York University Medical Center, New York, NY 10016, USA. Jeffrey.allen@nyumc.org
Donahue
Bernadine
B
Mehta
Minesh
M
Miller
Douglas C
DC
Rorke
Lucy B
LB
Jakacki
Regina
R
Robertson
Patricia
P
Sposto
Richard
R
Holmes
Emi
E
Vezina
Gilbert
G
Muraszko
Karin
K
Puccetti
Diane
D
Prados
Michael
M
Chan
Ka-Wah
KW
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D016190:Carboplatin / Q000008:administration & dosage; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
D016179:Granulocyte Colony-Stimulating Factor; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; D002945:Cisplatin