COMBINED TREATMENT WITH DACARBAZINE, CISPLATIN, FOTEMUSTINE AND TAMOXIFEN IN METASTATIC MALIGNANT-MELANOMA

The combination of dacarbazine (DTIC), cisplatin (DDP), carmustine and tamoxifen (TAM) has been reported to yield a high rate of response in patients with metastatic melanoma, but responders often experience in tracranial recurrences. As fotemustine (FOT) has demonstrated activity on cerebral metastases, the rationale of this study was to replace ca rmustine by FOT in this four-drug regimen. Twenty patients with metast atic melanoma received FOT (100 mg/m(2)) on days 1 and 8, DTIC (220 mg /m(2) per day) and DDP (25 mg/m(2) per day) from day 1 to day 3 and fr om day 28 to day 30, and continuous daily treatment with TAM (20 mg/da y). If stabilization or response was observed at the end of the 8th we ek, patients received maintenance courses of FOT on day 1, and DTIC (2 20 mg/m(2) per day) and DDP (25 mg/m(2) per day) on days 1 to 3. Ninet een patients were evaluable. Of these, six had brain metastases. The o verall response rate was 10.5% (two out of 19); both of the responders had only partial responsers. The best responding site was lung. No re sponse was obtained in the four patients with evaluable brain metastas es, but no patient had therapy failure due to new brain metastases. Th e median overall survival was 5 months (range 1-45 months). Toxicity w as mainly haematological. The use of this combination is not recommend ed. (C) 1998 Lippincott-Raven Publishers.