222. Results and toxicity of immunotherapy with genetically modified tumor vaccine (GMTV) combined with brain metastases irradiation in melanoma patients

Brain metastases are associated with poor prognosis. Median survival of such melanoma patients is 4 month. Standard treatment comprises palliative radiation therapy or palliative excision of solitary metastases in selected patients. Only patients with resected solitary metastases live a few months longer. The aim of this study was to asses results and toxicity of combined treatment with GMTV and irradiation in melanoma patients, who developed brain metastases. Since 1996 in Department of Cancer Immunology Great Poland Cancer Centre a group of 250 melanoma patients was treated with GMTV consisted of allogenic melanoma cell lines Mich1 and Mich2 modified with IL-6 and sIL-6R genes or fusiongene lL-6/sIL-6R. All patients were stage III and IV (AJCC). Before or during the immunization 22 patients presented symptoms of brain metastases. All patients were irradiated with the doses 30–39 Gy, using 3 Gy/fraction, 5 fractions/week. Toxicity and clinical results (CT, OS) were evaluated. In part of patients CTL and NK cytotoxicity and Th1 vs. Th2 profiles were evaluated in vitro. Side effects of irradiation were tolerable, 0–2 degree according to WHO criteria (standard dexamethasone treatment in all patients). There were no radiation encephalopathy or radiation necrosis. In 12/22 patients stabilization or partial remission were observed. Overall survival measured from brain metastases diagnosis ranged from 2 to 20 months. Median survival was 9 months. In 12 responder patients median survival was 13 months, ranged from 7 to 20 months. In 10 remaining patients median survival was 4 months. There were no differences in CTL activity but we noticed changes in NK activity and Th1/Th2 ratio (pooled in Th1 direction) after irradiation. Radiotherapy combined with GMTV compared with radiotherapy alone prolongs survival in melanoma patients, who developed brain metastases.