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Histamine in immunotherapy of advanced melanoma: a pilot study.

Journal article
Authors Kristoffer Hellstrand
Peter Naredi
Per Lindnér
Kent Lundholm
Carl-Magnus Rudenstam
Svante Hermodsson
Mats Asztely
Lars-Olof Hafström
Published in Cancer immunology, immunotherapy : CII
Volume 39
Issue 6
Pages 416-9
ISSN 0340-7004
Publication year 1994
Published at Institute of Surgical Sciences, Department of Surgery
Institute of Laboratory Medicine, Dept of Clinical Virology
Pages 416-9
Language en
Keywords Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, therapeutic use, Female, Histamine, therapeutic use, Humans, Interferon-alpha, administration & dosage, Interleukin-2, administration & dosage, Male, Melanoma, therapy, Middle Aged, Pilot Projects
Subject categories Cancer and Oncology


Sixteen patients with advanced metastatic malignant melanoma were treated with a high-dose infusion of interleukin-2 (IL-2; 18 x 10(6) IU/m-2 day-1) together with daily subcutaneous (s.c.) injections of interferon alpha (IFN alpha; 3 x 10(6) U/m-2 day-1) in 5-day cycles. Nine of these patients were given histamine (1 mg s.c.) twice daily during treatment with IL-2 and IFN alpha. In the seven patients who did not receive histamine, one partial response (that is a reduction of more than 50% in the total tumour burden) was observed in a patient with skin and lymph node melanoma. In the eight histamine-treated patients evaluable for response, four partial responses were observed. Two other patients showed regression at one site of metastasis but tumours remained unchanged at other sites. Two histamine-treated patients showed complete resolution of extensive liver metastasis. Sites of response in histamine-treated patients also included the subcutis, lymph nodes, skeleton, spleen and muscle. Lung melanoma did not respond to histamine/IL-2/IFN alpha. Three patients with lung tumours responded with significant (more than 50%) reduction of the volume of soft-tissue tumours, suggesting that the response to histamine may be organotropic. Survival was significantly prolonged in patients receiving histamine. Our data suggest that treatment with histamine may improve the antitumour efficacy of immunotherapy in metastatic melanoma.

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