Dacarbazine and interferon-alpha 2a in advanced malignant melanoma: high response rate and prolongation of response duration occur in different patient subpopulations.

Abstract

Fifty-three evaluable patients with metastatic malignant melanoma were enrolled in a phase II prospective study designed to assess the response rate, time to progression and survival after dacarbazine (DTIC) and interferon-alpha 2a (IFN-alpha 2a) treatment in patients with local metastatic disease compared with patients with distant metastases. Patients received intravenous DTIC from day 1 at a dosage of 400-500 mg/m2, repeated every 21 days (in the case of good tolerance--25 patients--the dose was increased to 600-800 mg/m2) combined with subcutaneous IFN-alpha 2a (9 x 10(6) U three times/week, increased in the case of good tolerance to 15 x 10(6) U three times/week). Forty-two patients with distant metastases were compared with 11 patients who had local metastatic disease. Three complete (6%) and six partial (11%) responses were seen, with an overall response rate of 17% (95% confidence interval 8-29). Patients with local metastases had a higher response rate (50%) compared with patients with distant metastases (visceral involvement, mediastinal and para-aortic lymph node metastases) (10%; p = 0.01). The median overall survival was 4.5 months. The progression-free interval for responders with distant metastases was significantly longer (11 months), than for responders with local metastases (4.5 months) (p = 0.004). These results may suggest that the combination treatment DTIC/IFN-alpha has a greater benefit in terms of longer progression-free interval in responders with distant metastases.