PHASE-II CLINICAL-TRIAL OF RECOMBINANT ALPHA-2B INTERFERON AND 13-CISRETINOIC ACID IN PATIENTS WITH METASTATIC MELANOMA

Treatment for metastatic melanoma is limited by low response rates to single- or combination-agent chemotherapy. Recent studies have examine d the role of biologic modifiers and differentiating agents. This phas e II study examined the efficacy and toxicity of combining alpha-2b-in terferon (IFN gamma) and 13 cis retinoic acid (cRA) in the treatment o f metastatic malignant melanoma. Thirteen patients were treated with I FN alpha (5 x 10(6) units/m(2) three times weekly) and cRA (1 mg/kg pe r day). One patient with lung and adrenal metastases had a partial res ponse 6 months in duration and two patients had stabilization of lung metastases for 2 months. All other patients had progressive disease. T oxicity was substantial with all patients experiencing Eastern Coopera tive Oncology Group grade 1-2 fatigue, myalgias, anorexia, stomatitis, and cheilitis. In addition, serum cholesterol and triglycerides were elevated in all patients. Seven patients required 50% dose reductions because of hypertriglyceridemia, fatigue associated with a significant decline in performance status, and severe stomatitis with anorexia an d weight loss. One patient discontinued therapy because of a decline i n performance status. This study suggests this combination of cRA and IFN alpha is inactive in the treatment of metastatic melanoma and is a ssociated with substantial toxicity.