Effects of interferon-α, verpamil and dacarbazine in the treatment of advanced malignat melanoma

Treatment of patients with metastatic melanoma with either dacarbazine (DTIC) or interferon-alpha (IFNalpha) as single drugs, or in combination, results in a response rate of approximately 15-20%. This study evaluated the activity and toxicity following treatment with a combination of DTIC, IFNalpha2b and verapamil (VPL). Thirty patients with disseminated metastatic melanoma received DTIC 250 mg/m(2) on days 1-5 of a 4 week schedule, IFNalpha2b 3 MIU on days 1-5 each week, and VPL 80 mg three times a day throughout the cycle, until either disease progression or serious toxicity was observed. Among the 28 evaluable patients, there were four complete responses (CRs), five partial responses (PRs) and eight patients with stable disease (SD). The overall response rate (CR + PR) was 32%. Two patients with a CR were long-term survivors (45 and 34 months) and a third is still in complete remission after 49 months. The fourth CR patient relapsed and died with progressive brain metastases after 8 months. Among the eight patients with SD, one survived for 22 months and another for 34 months. Despite one toxic death, these results suggest that this treatment regimen is well tolerated and seems to be more effective than DTIC alone in a subset of patients. A controlled randomized study would be required to determine the value of adding VPL and IFNalpha2b to DTIC.