Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: a Children's Oncology Group Phase I/II study.
OBJECTIVE
We evaluated the feasibility of administering carboplatin as a radiosensitizer during craniospinal radiation therapy (CSRT) to patients with high-risk medulloblastomas (MBs) and supratentorial primitive neuroectodermal tumors, and we report the outcome in the subset with metastatic (M+) MB.


METHODS
After surgery, patients received 36 Gy CSRT with boosts to sites of disease. During radiation, patients received 15 to 30 doses of carboplatin (30-45 mg/m(2)/dose), along with vincristine (VCR) once per week for 6 weeks. Patients on regimen A received 6 months of maintenance chemotherapy (MC) with cyclophosphamide and VCR. Once the recommended phase II dose (RP2D) of carboplatin was determined, cisplatin was added to the MC (regimen B).


RESULTS
In all, 161 eligible patients (median age, 8.7 years; range, 3.1 to 21.6 years) were enrolled. Myelosuppression was dose limiting and 35 mg/m(2)/dose × 30 was determined to be the RP2D of carboplatin. Twenty-nine (36%) of 81 patients with M+ MB had diffuse anaplasia. Four patients were taken off study within 11 months of completing radiotherapy for presumed metastatic progression and are long-term survivors following palliative chemotherapy. Excluding these four patients, 5-year overall survival ± SE and progression-free survival ± SE for M+ patients treated at the RP2D on regimen A was 82% ± 9% and 71% ± 11% versus 68% ± 10% and 59% ± 10% on regimen B (P = .36). There was no difference in survival by M stage. Anaplasia was a negative predictor of outcome.


CONCLUSIONS
The use of carboplatin as a radiosensitizer is a promising strategy for patients with M+ MB. Early progression should be confirmed by biopsy.
Children's Hospital of Pittsburgh, 4401 Penn Ave., Pittsburgh, PA 15224, USA. regina.jakacki@chp.edu
Regina I
RI
Jakacki
Peter C
PC
Burger
Tianni
T
Zhou
Emiko J
EJ
Holmes
Mehmet
M
Kocak
Arzu
A
Onar
Joel
J
Goldwein
Minesh
M
Mehta
Roger J
RJ
Packer
Nancy
N
Tarbell
Charles
C
Fitz
Gilbert
G
Vezina
Joanne
J
Hilden
Ian F
IF
Pollack
D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D002528:Cerebellar Neoplasms / Q000628:therapy; D059248:Chemoradiotherapy; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation / Q000379:methods; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008527:Medulloblastoma / Q000556:secondary / Q000628:therapy*; D009381:Neoplasms, Radiation-Induced / Q000175:diagnosis / Q000453:epidemiology; D018242:Neuroectodermal Tumors, Primitive / Q000556:secondary / Q000628:therapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D013120:Spinal Cord Neoplasms / Q000556:secondary / Q000628:therapy*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D016190:Carboplatin