First-line high-dose chemotherapy +/- radiation therapy in patients with metastatic germ-cell cancer and brain metastases

Purpose: To examine the feasibility and efficacy of first-line high-dose ch emotherapy (HD-CTX) in patients with advanced metastatic germ-cell tumors ( GCT) and brain metastases. Patients and methods: Twenty-two patients with brain metastases at initial diagnosis were identified within a cohort of two hundred thirty-one consecu tive patients with advanced metastatic disease, entered on a German multice nter trial between January 1993 and July 1998. All patients received first- line HD-CTX with cisplatin-etoposide-ifosfamide (HD-VIP) followed by autolo gous stem-cell transplantation. Brain irradiation (BRT) with 30-50 Gy +/- 1 0 Gy boost was applied in patients with symptomatic CNS disease or as conso lidation in case of residual CNS lesions after HD-CTX. Results: A median number of 4 HD-CTX cycles (range 2-5) were applied to the 22 patients. Ten patients received HD-CTX alone and twelve patients were t reated with HD-CTX plus BRT. Median duration of WHO grade 4 granulocytopeni a and thrombocytopenia was seven and five days after each cycle, respective ly. Non-hematologic toxicity consisted mainly of mucositis/enteritis (WHO g rade 3-4 32%). Two early deaths occurred in twenty-two patients (one CNS-bl eeding/one sepsis). Fourteen of twenty patients achieved a CR/PRm- status. Twenty patients (91%) responded in the brain (55% CR/36% PR). Two-year prog ression-free and overall survival rates were 72% and 81%, respectively. The se survival rates are substantially higher compared to the available data i n the literature. Conclusions: High-dose chemotherapy with autologous stem-cell support +/- B RT appears to be feasible without increased therapy-related mortality in pa tients with advanced metastatic GCT and brain metastases. The results achie ved emphasize the high chemosensitivity of CNS metastases from GCT and sugg est a potential role for dose intensification. The dose of BRT in addition to HD-CTX may be tailored to the presence of clinical symptoms and the resp onse of CNS metastases to chemotherapy.