Combination of highly purified human leukocyte interferon alpha and 13-cis-retinoic acid for the treatment of metastatic melanoma.

The effect of 13-cis-retinoic acid and highly purified human leukocyte interferon alpha (Alphaferon) therapy for metastatic melanoma was studied. A group of 17 patients with disseminated malignant melanoma were treated over a 6-month period. They received 60 mg 13-cis-retinoic acid/day continuously and ten cycles of interferon alpha (IFN alpha). IFN was administered by subcutaneous injection, at a daily dose of 6 x 10(6) IU Alphaferon. The 5-day treatment period was followed by an IFN-free interval of 2 weeks. We were able to observe an overall response rate of 30% with 12% complete responses (2 out of 17 patients). Sites of response included the skin, lung, liver and lymph nodes. All responses have now lasted over 6 months. Therapy was generally well tolerated and could be performed on an outpatient basis. Side-effects of this combination therapy did not exceed the established side-effects of the two substances. We also studied 2'-5'-oligoadenylate synthetase, beta 2-microglobulin and neopterin levels during the whole treatment course. All patients were within the normal range before treatment and a sharp rise occurred during each IFN cycle. The maximum being observed 24 h after the third injection. This indicates a high biological activity of IFN alpha administered cyclically during the whole treatment course. This finding also corresponds well with the absence of neutralizing antibodies before and after the whole treatment period.