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; p. 1691
• 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: England Oxford Publishing Limited (England) 01.10.2007
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Dacarbazine - administration & dosage; Dacarbazine - adverse effects; Female; Histamine - administration & dosage; Histamine - adverse effects; Humans; Immunotherapy; Interferon alpha-2; Interferon-alpha - administration & dosage; Interferon-alpha - adverse effects; Interleukin-2 - administration & dosage; Interleukin-2 - adverse effects; Male; MEDICAL AND HEALTH SCIENCES; MEDICIN OCH HÄLSOVETENSKAP; Melanoma - drug therapy; Melanoma - mortality; Melanoma - pathology; Middle Aged; Multivariate Analysis; Neoplasm Staging; Recombinant Proteins
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdm331

The safety and efficacy of immunotherapy with histamine dihydrochloride (HDC), interleukin-2 (IL-2) and interferon-alpha2b (IFN) compared with dacarbazine (DTIC) in adult patients with stage IV melanoma was evaluated. 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(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(2) i.v. every 3 weeks. The primary endpoint was overall survival. 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. 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.