INTERFERON-ALPHA-2A DOES NOT IMPROVE RESPONSE OR SURVIVAL WHEN COMBINED WITH DACARBAZINE IN METASTATIC MALIGNANT-MELANOMA - RESULTS OF A MULTIINSTITUTIONAL AUSTRALIAN RANDOMIZED TRIAL

Following extensive phase II trials of the combination of dacarbazine and interferon-alpha2a we performed a prospective, randomized, control led trial of this combination versus dacarbazine alone as systemic the rapy for symptomatic, measurable metastatic malignant melanoma. The tw o treatment arms were well matched for age, sex, performance, status, relapse-free survival, prior therapy and sites of disease. Therapy con sisted 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 star ting at 3 mU dally on days 1-3, 9 mU dally on days 4-70, then 9 mU thr ee times per week. Therapy was continued for at least 6 months unless overt progressive disease was observed. Eighty seven patients were ran domized to the combination and 83 patients to dacarbazine alone. Respo nse rates were respectively, complete 7% and 2%, and partial 14% and 1 5%, for a total response rate of 21% (95% confidence limits 13-31%) an d 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 re spectively. Toxicity was worse in the combination arm, with more patie nts experiencing fatigue, nausea and anorexia, flu-like symptoms and n eutropenia. However quality of life was not significantly different in either group, except that fatigue, as measured at week 12 by LASA sca les, and activity, as measured by the functional living index, were bo th improved in the combination. We conclude from this study, which is the largest reported randomized trial to date, that the combination is not superior to single agent therapy.