Treatment of Malignant Carcinoid Tumors With Recombinant Interferon alfa-2b: Development of Neutralizing Interferon Antibodies and Possible Loss of Antitumor Activity

Abstract

Twenty patients with malignant carci-noid tumors were treated for 6 months with recombinant interferon alfa-2b(IFN α-2b; Intron-A; Schering Corp., Bloomfield, NJ) at a mean dose of 5.9 megaunits three times per week. Eleven of the 20 patients (55%) had a <50% reduction of tumor markers (urinary5-hydroxyindoleacetic acid or plasmaneuropeptide K), showing objective tu-mor response. Six patients (30%) had stable disease with no significant change in tumor markers or tumor size, and three (15%) had progressive disease with an increase in tumor markers andsize. These results are similar to those reported earlier for treatment with natural leukocyte IFN in patients with carcinoid tumors. Only two patients (35%)had a slight reduction of tumor size after 6 months of treatment. Three patients developed neutralizing antibodies to IFN a-2b. Two of these patients initially showed an objective response, which lasted until IFN anti-bodies developed. In one of these patients, a change to human leukocyte IFN resulted in normalization of antibody titers within 3 months, and the patient had a second objective clinical response. There was no correlation between development of IFN antibod-ies and development of autoimmune phenomena such as increased titers of antinuclear antibodies or thyroid auto antibodies. IFN a-2b seems to be as potent as human leukocyte IFN in the treatment of patients with malignant carcinoid tumors, but it is important to recognize that antibodies neutralizing IFN may develop in some patients, with concomitant loss of antitumor effects. A change to natural leukocyte IFN might be beneficial in these pa-tients. [J Natl Cancer Inst 81:531-535,1989]