BACKGROUND: The treatment results of metastatic melanoma are miserable if the tumor has spread beyond the soft tissue and lung, in particular, if dacarbazine (DTIC)-based therapy has failed. Platinum analogs and vinca alkaloids have shown some activity in melanoma. Interleukin-2 (IL-2) may augment the efficacy of chemotherapy. PATIENTS AND METHODS: A prospective phase II pilot study was conducted to evaluate the efficacy and tolerability of a regimen which contained carboplatin (450 mg/m(2) on day 1), vinorelbine (30 mg/m(2) on day 1) and IL-2 (9 MU subcutaneously once daily on days 2-5 and 9-12) in metastatic melanoma. Twenty-two patients (11 men, 11 women; median age 56 years) were eligible, of whom 13 had cutaneous, 6 ocular and 3 unknown primary melanoma. Seventeen patients (77%) had liver metastases and an equal number had received prior chemotherapy and/or interferon-alfa for recurrent disease. RESULTS: One partial response was recorded, yielding a response rate of 4.5% . Nine patients had stable disease for a median of 6.0 months (range 3.0-8.6 months). The median time to progression for all patients was 1.8 months (range 0.7-8.6 months) and the median survival was 7.2 months (range 1.4-42.0 months). Toxicity was moderate but manageable. Myelosuppression was the most significant adverse event. CONCLUSION: This regimen may offer clinical benefit for melanoma patients with poor prognosis as second-line therapy after DTIC has failed.