Preradiation chemotherapy in advanced medulloblastoma. A Pediatric Oncology Group pilot study.

BACKGROUND

Children diagnosed with medulloblastoma whose tumor involves the brain stem or has spread through the cerebrospinal fluid pathways to other areas of the brain or spinal cord have a poor prognosis despite therapy with surgery, craniospinal irradiation (CSI), and chemotherapy. Preradiation chemotherapy may improve the outlook for these patients.

METHODS

To further study the role and feasibility of preradiation chemotherapy, children between the ages of 4 and 21 years diagnosed with advanced medulloblastoma and measurable disease were enrolled in the Pediatric Oncology Group 8695 study. Patients were treated with a 9-week course of vincristine, cisplatin, and cyclophosphamide followed by CSI. Imaging films were reviewed centrally for eligibility and response to chemotherapy. Toxicity to chemotherapy and radiation as well as delays and modifications in subsequent CSI were recorded.

RESULTS

Thirteen of 30 fully evaluable patients achieved complete or partial response (43%) to chemotherapy. Toxicity was mostly fever and neutropenia after cyclophosphamide, which is predictable and tolerable. Radiation therapy was delivered in full doses and volumes in most patients but was delayed in its start in most patients. Central review of films revealed frequent use of different imaging modalities at baseline and after therapy, making accurate assessment of tumor response difficult.

CONCLUSIONS

Preradiation chemotherapy with vincristine, cisplatin, and cyclophosphamide is active in patients with advanced medulloblastoma but should be modified to minimize the risk of progressive disease while on therapy and to avoid delays in starting radiation therapy. Consistent use of the same neuroimaging modality is essential in documenting response.