A Phase II feasibility study of oral etoposide given concurrently with radiotherapy followed by dose intensive adjuvant chemotherapy for children with newly diagnosed high-risk medulloblastoma (protocol POG 9631): A report from the COG
Standard treatment at Children's Oncology Group (COG) institutions for children over the age of 3 years with high-risk medulloblastoma currently includes craniospinal radiation with concurrent chemotherapy, followed by maintenance chemotherapy. This is a Phase II feasibility study from the COG to assess if using oral etoposide concurrently with radiation therapy could improve survival.
This is a cohort study that enrolled patients with high-risk medulloblastoma. All patients underwent surgical debulking, followed by craniospinal radiation and daily oral etoposide on days 1-21 and 29-49 at 50 mg/m^2 per day. A dose limiting toxicity of dysphagia/esophagitis was noted with this dose of etoposide, and therefore the final 38 patients were treated with a lower dose of etoposide (35 mg/m^2). After radiotherapy, the patients received further maintenance chemotherapy.
This study enrolled 53 patients between the ages of 3 and 21 who had high-risk medulloblastoma between November 1998 and October 2002. There was an excellent response to the radiation and oral etoposide, with 19 (40.4%) showing a complete response, 24 (51.1%) showing a partial response and four (8.5%) with no recorded response. Overall 2 and 5 year overall survival (OS) was 80.9% and 76.6% respectively, which is comparable to previous studies. There was no significant difference in outcome between the higher and lower dose treatment groups.
The limitations of this study include the small size of the patient cohort, and also the lack of specific histologic or molecular stratification of tumors. This trial was also run in an era before molecular subgroups were known which limits its current generalizability.