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 carcinoid tumors were treated for 6 months with recombinant interferon alfa-2b (IFN alpha-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 greater than 50% reduction of tumor markers (urinary 5-hydroxyindoleacetic acid or plasma neuropeptide K), showing objective tumor 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 and size. 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 alpha-2b. Two of these patients initially showed an objective response, which lasted until IFN antibodies 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 antibodies and development of autoimmune phenomena such as increased titers of antinuclear antibodies or thyroid autoantibodies. IFN alpha-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 patients.