HISTAMINE IN IMMUNOTHERAPY OF ADVANCED MELANOMA - A PILOT-STUDY

Sixteen patients with advanced metastatic malignant melanoma were trea ted with a high-dose infusion of interleukin-2 (IL-2; 18x10(6) IU/m(-2 ) day(-1)) together with daily subcutaneous (s.c.) injections of inter feron a (IFN alpha; 3x10(6) U/m(-2) day(-1)) in 5-day cycles. Nine of these patients were given histamine (1 mg s.c.) twice daily during tre atment with IL-2 and IFN alpha. In the seven patients who did not rece ive histamine, one partial response (that is a reduction of more than 50% in the total tumour burden) was observed in a patient with skin an d lymph node melanoma. In the eight histamine-treated patients evaluab le for response, four partial responses were observed. Two other patie nts showed regression at one site of metastasis but tumours remained u nchanged at other sites. Two histamine-treated patients showed complet e resolution of extensive liver metastasis. Sites of response in hista mine-treated patients also included the subcutis, lymph nodes, skeleto n, 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, sugge sting that the response to histamine may be organotropic. Survival was significantly prolonged in patients receiving histamine. Our data sug gest that treatment with histamine may improve the antitumour efficacy of immunotherapy in metastatic melanoma.