The effect of tamoxifen and cisplatin on the disease-free and overall survival of patients with high risk malignant melanoma

The adjuvant treatment of high-risk malignant melanoma remains problematic. Previously we reported moderate success in the treatment of metastatic dis ease using tamoxifen, cisplatin, dacarbazine and carmustine. Based upon dat a that suggested tamoxifen and cisplatin were the active agents in this reg imen, we initiated a phase II trial of this combination in the adjuvant set ting. We treated 153 patients with 4 cycles of tamoxifen (160 mg day(-1), d ays 1-7) and cisplatin (100 mg m(-2), day 2) for 28-day intervals, Patients received an anti-nausea regimen of dexamethasone with ondansetron or grani setron. During the first 2 years of follow-up, patients were evaluated ever y 2 months with a history, physical exam, laboratory work and computed tomo graphy scans of the chest, abdomen and pelvis every 4 months. Thereafter, p atients were evaluated every 3 months and radiographic studies were perform ed if necessary. Currently, with a median follow-up of 36 months. the disea se-free survival (DFS) is 68.4% and overall survival (OS) is 84.5%, Kaplan- Meier analysis predicts a 5-year DFS of 62% with an OS of 79%. Relapses aft er 20 months have been rare. No effect of gender or number of positive lymp h nodes was noted, however, stage of disease prior treatment was a factor. The major toxicity proved to be gastrointestinal in nature with nausea the most prevalent symptom. Minimal renal, haematologic and neurologic toxicity occurred. These preliminary results suggest that there is a positive impac t of tamoxifen and cisplatin on both the DFS and OS of high-risk malignant melanoma patients. The 5-year projected DFS and OS compare favourably with those reported for the ECOG 1684 trial and warrant confirmation in a prospe ctive randomized trial. (C) 2000 Cancer Research campaign.