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The therapy of metastatic melanoma is limited by poor responses to known chemotherapeutic agents. The report of Mulder et al. (Proc ASCO 1992; 11: 347) raised the possibility of the known interaction between 5-fluorouracil and interferon-alpha2a improving response rates in melanoma. This study was designed to examine the effects of 5-fluorouracil plus interferon-alpha2a alone without the confounding effects of dacarbazine. Doses were chosen based on the earlier study rather than the higher doses used in colon cancer. Therapy for metastatic melanoma with 5-fluorouracil and interferon-alpha2a is manageable in terms of toxicity. The major toxicities were lethargy, nausea/anorexia and flu-like symptoms. These were thought to be primarily attributable to interferon-alpha2a. Only one case of severe diarrhoea occurred. The response rate of 14% is similar to the reported results of interferon-alpha2a treatment alone. On these data, there is no evidence of synergy using this dose and schedule.

Following extensive phase II trials of the combination of dacarbazine and interferon-alpha 2a we performed a prospective, randomized, controlled trial of this combination versus dacarbazine alone as systemic therapy for symptomatic, measurable metastatic malignant melanoma. The two treatment arms were well matched for age, sex, performance, status, relapse-free survival, prior therapy and sites of disease. Therapy consisted of dacarbazine given in combination in escalating doses of 200 mg/m2, 400 mg/m2 and 800 mg/m2 i.v. every 3 weeks, or alone at 800 mg/m2 i.v. every 3 weeks. Interferon was administered subcutaneously starting at 3 mU daily on days 1-3, 9 mU daily on days 4-70, then 9 mU three times per week. Therapy was continued for at least 6 months unless overt progressive disease was observed. Eighty seven patients were randomized to the combination and 83 patients to dacarbazine alone. Response rates were respectively, complete 7% and 2%, and partial 14% and 15%, for a total response rate of 21% (95% confidence limits 13-31%) and 17% (95% confidence limits 10-27%). Median duration of response was 258 and 286 days, and survival of the whole groups 229 and 269 days respectively. Toxicity was worse in the combination arm, with more patients experiencing fatigue, nausea and anorexia, flu-like symptoms and neutropenia. However quality of life was not significantly different in either group, except that fatigue, as measured at week 12 by LASA scales, and activity, as measured by the functional living index, were both improved in the combination.(ABSTRACT TRUNCATED AT 250 WORDS)