Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma.
OBJECTIVE
To evaluate the feasibility of and response rate to an intensified induction chemotherapy regimen for young children with newly diagnosed high-risk or disseminated medulloblastomas.


METHODS
From January 1997 to March 2003, 21 patients with high-risk or disseminated medulloblastoma were enrolled. After maximal surgical resection, patients were treated with five cycles of vincristine (0.05 mg/kg/wk x three doses per cycle for three cycles), cisplatin (3.5 mg/kg per cycle), etoposide (4 mg/kg/d x 2 days per cycle), cyclophosphamide (65 mg/kg/d x 2 days per cycle) with mesna, and methotrexate (400 mg/kg per cycle) with leucovorin rescue. Following induction chemotherapy, eligible patients underwent a single myeloablative chemotherapy cycle with autologous stem-cell rescue.


RESULTS
Significant toxicities of this intensified regimen, including gastrointestinal and infectious toxicities, are described. Among the 21 patients enrolled, there were 17 complete responses (81%), two partial responses, one stable disease, and one progressive disease. The 3-year event-free survival and overall survival are 49% (95% CI, 27% to 72%) and 60% (95% CI, 36% to 84%), respectively.


CONCLUSIONS
This intensified induction chemotherapy regimen is feasible and tolerable. With the majority of patients with disseminated medulloblastoma having M2 or M3 disease at diagnosis, the encouraging high response rate of this intensified induction regimen suggests that such an addition of methotrexate should be explored in future studies.
Chi
Susan N
SN
Division of Pediatric Oncology, New York University Medical Center, New York, NY, USA. susan_chi@dfci.harvard.edu
Gardner
Sharon L
SL
Levy
Adam S
AS
Knopp
Edmond A
EA
Miller
Douglas C
DC
Wisoff
Jeffrey H
JH
Weiner
Howard L
HL
Finlay
Jonathan L
JL
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D002528:Cerebellar Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D015080:Mesna / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D015080:Mesna; D002945:Cisplatin; D002955:Leucovorin; D008727:Methotrexate