Treatment of children with diffuse intrinsic brain stem glioma with radiotherapy, vincristine and oral VP-16: A children's oncology group phase II study

Background. The prognosis for children with brain stem glioma remains grim. Based on studies suggesting efficacy of vincristine and oral VP-16, The Pediatric Oncology Group (POG, now part of the Children's Oncology Group) conducted a study using these agents in combination with standard external beam radiation for children with newly diagnosed brain stem glioma. Methods. Children were eligible for the study if they 3-21 years of age, had MRI-evidence of a diffuse intrinsic pontine glioma, and had neurologic deficits of <6 months duration. Patients received local radiotherapy to a dosage of 54 Gy. Chemotherapy consisted of two 28-day cycles of vincristine, 1.5 mg/m(2), days 1, 8, and 15 and oral VP-16, 50 mg/m(2), days 1-21, starting concurrent with radiation, and continuing for ten cycles following radiation. Results. Of the 31 children enrolled, 30 were eligible and evaluable for survival and toxicity. Their median age was 8 years (range 3-14 years). Seven patients (23%) had a partial response following radiation, 18 (60%) had stable disease, 2 (7%) had progressive disease, and response in 3 patients (10%) was not measured. All 30 children have died. Overall survival at I year was 27 7% and at 2 years, 3 +/- 2%. The median survival was 9 months (range 3-36 months). Hematologic toxicity was significant; other toxicities included constipation, mucositis, emesis, and infection. Conclusion. The addition of vincristine and oral VP-16 to standard external beam radiation causes moderate toxicity and does not improve survival of children with diffuse intrinsic brain stem glioma.