Results of a multicenter randomized study to evaluate the safety and efficacy of combined immunotherapy with interleukin-2, interferon- alpha 2b and histamine dihydrochloride versus dacarbazine in patients with stage IV melanoma

• Published in: Annals of oncology Vol. 18; no. 10; pp. 1691 - 1697
• Main Authors: Middleton, M, Hauschild, A, Thomson, D, Anderson, R, Burdette-Radoux, S, Gehlsen, K, Hellstrand, K, Naredi, P
• Format: Journal Article
• Language: English
• Published: 01.10.2007
• ISSN: 0923-7534
• DOI: 10.1093/annonc/mdm331

BACKGROUND: The safety and efficacy of immunotherapy with histamine dihydrochloride (HDC), interleukin-2 (IL-2) and interferon- alpha 2b (IFN) compared with dacarbazine (DTIC) in adult patients with stage IV melanoma was evaluated. PATIENTS AND METHODS: Two hundred and forty-one patients were randomized to either receive repeated 4-week cycles of IFN [3 MIU, s.c., once daily for 7 days], IL-2 (2.4 MIU/m super(2), s.c., twice a day for 5 days) and HDC (1 mg, s.c., twice a day for 5 days) or DTIC 850 mg/m super(2) i.v. every 3 weeks. The primary endpoint was overall survival. RESULTS: Median survival was longer for patients receiving HDC/IL-2/IFN (271 days) than for patients receiving DTIC (231 days), but this did not achieve statistical significance. Four patients receiving HDC/IL-2/IFN and nine receiving DTIC experienced at least one grade 4 adverse event. Striking differences in overall survival were observed between countries participating in the study. CONCLUSION: Treatment with HDC/IL-2/IFN was safely administered on an outpatient basis, but this immunotherapeutic regimen did not improve upon the response rate and overall survival seen with DTIC.