Radiotherapy followed by high dose busulfan and thiotepa - A prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas

BACKGROUND. The role of high dose chemotherapy (HDC) in patients with pedia tric brain tumors currently is ill-defined. The purpose of this pilot study was to assess the feasibility and the benefit of HDC after radiotherapy in a group of children with newly diagnosed diffuse pontine gliomas. METHODS. Patients eligible for study were ages 3-18 years with diffuse intr insic tumors arising in the pens, who were not treated previously with radi otherapy or chemotherapy. Histologic confirmation was not mandatory, provid ed clinical findings and magnetic resonance imaging were typical. Patients were given focal radiotherapy followed 2-3 months later by HDC. Busulfan (1 50 mg/m(2) on Days 8, 7, 6, and 5) and thiotepa (300 mg/m(2) on Days 4, 3, and 2) were administered prior to autologous bone marrow transplantation. S urvival was the endpoint, and the statistical procedure was based on sequen tial subgroup analysis. RESULTS. Thirty-six patients were entered on to the study, 12 of whom under went stereotactic biopsy or open surgery at the time of diagnosis. One pati ent eventually was excluded due to inappropriate eligibility criteria. AU 3 5 eligible patients received irradiation. Early progression (9 patients) an d parental refusal (2 patients) precluded the use of HDC in 11 patients. Th ree patients died of HDC-related complications. All 21 patients who survive d HDC eventually died of disease progression. The median survival time was 10 months for the study group. The median survival time in the subgroup of patients who received HDC was 10 months (range, 3-26 months). Statistical a nalysis did nor suggest any evidence of survival benefit. CONCLUSIONS. For patients with diffuse pontine gliomas, survival using this aggressive treatment modality does not appear to be any better than that r eported for conventional radiotherapy. (C) 2000 American Cancer Society.