Outcome of patients with recurrent medulloblastoma or central nervous system germinoma treated with low dose continuous intravenous etoposide along with dose‐intensive chemotherapy followed by autologous hematopoietic stem cell rescue

Abstract

Adults and children with recurrent malignant central nervous system (CNS) tumors have a poor prognosis despite high dose chemotherapy with a conventional stem cell rescue regimen. In this study we evaluated the results of low dose, continuous infusion etoposide over 21 days added to a conventional high-dose regimen of carboplatin and thiotepa in eight patients with relapsed pediatric CNS tumors. Patients with high risk CNS tumors were treated with etoposide 25 mg/m(2)/day by continuous intravenous (IV) infusion from day -22 to day -2, carboplatin 667 mg/m(2)/dose IV (or area under the curve = 9 mg/ml/min according to the Calvert formula on days -8, -7, and -6, and thiotepa 300 mg/m(2)/dose IV on days -5, -4, and -3, followed by autologous hematopoietic stem cell rescue on day 0. Eight adults and children, with a mean age of 12.9 years (age range 5.6-27.8 years), with relapsed primary CNS tumors (metastatic medulloblastoma (7), germinoma (1)), were enrolled. The mean survival post-transplant was 4.8+ years, (range 8-160+ months). The 2- and 5-year overall survival rates were 75% and 50% respectively. None of the survivors required additional salvage irradiation. The strategy of low dose chronic exposure to a topoisomerase inhibitor along with ablative carboplatin and thiotepa with stem cell rescue showed promising survival outcomes in these relapsed patients. This treatment strategy deserves further evaluation in a larger group of high-risk or relapsed primary CNS tumors.