Outcome of children with metastatic medulloblastoma treated with carboplatin during craniospinal radiotherapy: a Children's Oncology Group Phase I/II study.

Abstract

PURPOSE:

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.

PATIENTS AND 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.

CONCLUSION:

The use of carboplatin as a radiosensitizer is a promising strategy for patients with M+ MB. Early progression should be confirmed by biopsy.

• Authors: Regina I Jakacki, Peter C Burger, Tianni Zhou, Emiko J Holmes, Mehmet Kocak, Arzu Onar, Joel Goldwein, Minesh Mehta, Roger J Packer, Nancy Tarbell, Charles Fitz, Gilbert Vezina, Joanne Hilden, Ian F Pollack
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 30 Issue 21 Pg. 2648-53 (Jul 20 2012) ISSN: 1527-7755 [Electronic] United States
• PMID: 22665539 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents
• Radiation-Sensitizing Agents
• Carboplatin

Topics

• Adolescent
• Antineoplastic Agents (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Brain Neoplasms (pathology, therapy)
• Carboplatin (administration & dosage, adverse effects)
• Cerebellar Neoplasms (therapy)
• Chemoradiotherapy
• Child
• Child, Preschool
• Cranial Irradiation (methods)
• Disease-Free Survival
• Drug Administration Schedule
• Feasibility Studies
• Female
• Humans
• Incidence
• Kaplan-Meier Estimate
• Male
• Medulloblastoma (secondary, therapy)
• Neoplasms, Radiation-Induced (diagnosis, epidemiology)
• Neuroectodermal Tumors, Primitive (secondary, therapy)
• Radiation-Sensitizing Agents (administration & dosage, adverse effects)
• Spinal Cord Neoplasms (secondary, therapy)
• Treatment Outcome