Dacarbazine and interferon alpha with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG)

In several phase II-trials encouraging tumour responses rates in advanced m etastatic melanoma (stage IV; AJCC-classification) have been reported for t he application of biochemotherapy containing interleukin 2. This study was designed to compare the efficacy of therapy with dacarbazine (DTIC) and int erferon alpha (IFN-alpha) only to that of therapy with DTIC and IFN-alpha w ith the addition of interleukin 2 (IL-2) in terms of the overall survival t ime and rate of objective remissions and to provide an elaborated toxicity profile for both types of therapy. 290 patients were randomized to receive either DTIC (850 mg/m(2) every 28 days) plus IFN-alpha 2a/b (3 MIU/m(2), tw ice on day 1, once daily from days 2 to 5; 5 MIU/m(2) 3 times a week from w eek 2 to 4) with or without IL-2 (4.5 MIU/m(2) for 3 hours i.v. on day 3; 9 .0 MIU/m(2) i.v. day 3/4; 4.5 MIU/m(2) s.c. days 4 to 7). The treatment pla n required at least 2 treatment cycles (8 weeks of therapy) for every patie nt. Of 290 randomized patients 281 were eligible for an intention-to-treat analysis. There was no difference in terms of survival time from treatment onset between the two arms (median 11.0 months each). In 273 patients treat ed according to protocol tumour response was assessable. The response rates did not differ between both arms (P = 0.87) with 18.0% objective responses (9.7% PR; 8.3% CR) for DTIC plus IFN-alpha as compared to 16.1% (8.8% PR; 7.3% CR) for DTIC, IFN-alpha and IL-2. Treatment cessation due to adverse r eactions was significantly more common in patients receiving IL-2 (13.9%) t han in patients receiving DTIC/IFN-alpha only (5.6%). In conclusion, there was neither a difference in survival time nor in tumour response rates when IL-2, applied according to the combined intravenous and subcutaneous sched ule used for this study, was added to DTIC and IFN-alpha. However, toxicity was increased in melanoma patients treated with IL-2. Further phase III tr ials with continuous infusion and higher dosages must be performed before a ny final conclusions can be drawn on the potential usefulness of IL-2 in bi ochemotherapy of advanced melanoma. (C) 2001 Cancer Research Campaign.