Phase II trial of primary chemotherapy followed by reduced-dose radiation for CNS germ cell tumors

Purpose: A prospective phase II study was initiated to assess the response rate, survival, and late effects of treatment in patients with newly diagno sed CNS germ cell tumors (GCT), using etoposide plus cisplatin followed by radiation therapy prescribed by extent of disease, histology, and response to chemotherapy. Patients and Methods: Seventeen patients aged 8 to 24 years with histologic ally proven CNS GCT received etoposide (100 mg/m(2)/d) plus cisplatin (20 m g/m(2)/d) daily for 5 days every 3 weeks for four cycles, followed by radia tion therapy Nine patients had germinomas; eight had mixed GCT. Four patien ts (three with germinomas and one with mixed GCT) presented with leptomenin geal dissemination. Results: Radiographically, 14 of 17 patients were assessable for response; 11 patients experienced complete regression, and three had major partial re gression before radiation. Six of seven assessable patients with elevated C SF revels of alpha-fetoprotein or beta-human chorionic gonadotropin had nor malization with chemotherapy alone; all normalized with combined chemothera py and radiation therapy. All 17 patients are alive without evidence of dis ease (median followup, 51 months). One patient developed a relapse in the s pinal leptomeninges and was rendered free of disease with spinal radiation more than 5 years ago. One patient developed carotid stenosis requiring sur gery. Thus far, only minimal long-term deterioration in neuro-cognitive fun ction has been detected as a consequence of protocol treatment. Conclusion: Conventional-dose intravenous chemotherapy with etoposide and c isplatin can effect tumor regression in a high proportion of patients with CNS GCT, including those with leptomeningeal metastases. Acute and rang-ter m toxicities are acceptable, Progression-free survival and overall survival are excellent. (C) 1999 by American Society of Clinical Oncology.