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.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Grodman
Howard
H
Floating Hospital for Children, Tufts Medical Center, Boston, Massachusetts 02111, USA. hgrodman@tuftsmedicalcenter.org
Wolfe
Lawrence
L
Kretschmar
Cynthia
C