Clinical Correlative Studies In Primary Central Nervous System Germ Cell Tumors: The Third International CNS Germ Cell Tumor Study Group Protocol

OBJECTIVES:

• Determine the two-year event-free survival of patients with primary CNS germ cell tumors treated with carboplatin, etoposide, cyclophosphamide, and filgrastim (G-CSF) with or without radiotherapy and/or high-dose chemotherapy with autologous bone marrow or peripheral blood stem cell transplantation.
• Determine the prognostic significance of slow-responding tumor marker normalization in patients treated with this regimen.
• Determine the prognostic significance of syncytiotrophoblastic giant cell component and cerebrospinal fluid beta-human chorionic gonadotropin elevation in patients treated with this regimen.
• Assess the early and late endocrinologic, neuropsychometric, and quality of life sequelae in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to risk status (low vs intermediate or high).

Regimen A (Low-risk patients)

• Chemotherapy: Patients receive carboplatin IV over 4 hours and etoposide IV over 2 hours on days 1-2 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 3 and continuing until blood counts recover (course 1). Patients also receive cyclophosphamide IV over 1 hour and etoposide IV over 2 hours on days 22 and 23 and G-CSF SC once daily beginning on day 24 and continuing until blood counts recover (course 2).
• Patients with complete response (CR) to initial chemotherapy receive 2 additional courses of chemotherapy as above and then proceed to observational phase. Patients with partial response (PR) to initial chemotherapy receive 2 additional courses of chemotherapy as above.
• Patients with CR after additional chemotherapy receive another 2 additional courses of chemotherapy as above and then proceed to observational phase. Patients with PR after additional chemotherapy undergo biopsy and/or resection of residual tumor.
• Patients with evidence of malignant germ cell tumor (GCT) on resection undergo radiotherapy. Patients with no evidence of malignant GCT on resection but with scar, fibrosis, or mature teratoma receive 2 additional courses of chemotherapy as above and then proceed to observational phase. Patients with no evidence of malignant GCT on resection but with immature teratoma receive carboplatin IV over 4 hours, cyclophosphamide IV over 1 hour, and etoposide IV over 2 hours on days 1-2 and 22-23. Patients who underwent complete resection of residual tumor proceed to observational phase. Patients who underwent a biopsy only or an incomplete resection of residual tumor undergo radiotherapy.