ISOTRETINOIN AND RECOMBINANT INTERFERON ALFA-2A THERAPY OF METASTATICMALIGNANT-MELANOMA

Twenty-five patients with metastatic malignant melanoma were treated w ith isotretinoin (13-cis-retinoic acid) orally at 1 mg/kg daily and re combinant interferon alfa-2a (IFN-alpha) subcutaneously at 3 million u nits daily for 16-48 weeks. Therapy was well tolerated; fatigue and hy perlipidemia were the most frequent dose-limiting toxicity and necessi tated dose reductions in 14 patients. Two patients achieved a complete response, and 3 responded partially for a total response rate of 20% (95% confidence interval: 4-36%). Responses occurred primarily in pati ents with limited tumor burden and disease confined to the skin and ly mph nodes. Significant elevations in peripheral blood 2'-5'-oligoadeny late synthetase activity and natural killer activity were observed wit h therapy. The magnitude of these changes, however, was not predictive of response. Biopsy specimens oftwo responding lesions showed extensi ve necrosis of tumor. One specimen showed large aggregates of melanoph ages in association with tumor. The combination of isotretinoin and IF N-alpha is an active, easily administered regimen with acceptable toxi city for metastatic malignant melanoma.