Primary chemotherapy for intracranial germ cell tumors: results of the third international CNS germ cell tumor study

Abstract

Background: The treatment of central nervous system (CNS) germ cell tumors (GCT) remains controversial. The purpose of this study was to demonstrate efficacy of a chemotherapy only strategy, with less morbidity, when compared to regimens with irradiation.

Methods: Between January 2001 and December 2004 newly diagnosed patients with CNS GCT were treated with one of two risk-tailored chemotherapy regimens. Twenty-five patients aged 4 months to 24.5 years were stratified: Regimen A consisted of 4-6 cycles of carboplatin/etoposide alternating with cyclophosphamide/etoposide for low risk (LR) localized germinoma with normal cerebrospinal fluid (CSF) and serum tumor markers. Regimen B consisted of 4-6 cycles of carboplatin/cyclophosphamide/etoposide for intermediate-risk (IR) germinoma with positive human chorionic gonadotrophin-beta (HCGbeta) and/or CSF HCGbeta <50 mIU/ml and high-risk (HR) biopsy-proven non-germinomatous malignant elements (MMGCT) or elevated serum/CSF alpha-fetoprotein and/or HCGbeta serum/CSF >50 mIU/ml.

Results: Eleven patients were classified as LR, 2 IR, and 12 HR. Seventeen (68%) patients achieved complete radiographic and marker responses after two courses and 19 (76%) after four courses of chemotherapy. Eleven patients relapsed at a mean of 30.8 months; eight of them subsequently received irradiation. The 6-year event free and overall survival for the 25 patients was 45.6% and 75.3%, respectively.

Conclusion: These intensive chemotherapy regimens proved less effective than irradiation containing regimens. Our results indicate that, at the present time, standard treatment for CNS GCT continues to include irradiation either alone or combined with chemotherapy for pure germinomas and with chemotherapy for those with MMGCT.