AUTOIMMUNITY AFTER ALPHA-INTERFERON THERAPY FOR MALIGNANT CARCINOID-TUMORS

Objective: To determine the incidence of autoantibodies and autoimmune disease and their influence on therapeutic results during alpha-interferon treatment in patients with malignant midgut carcinoid tumors. Design: Consecutive sample of patients. Setting: University hospital. Patients: One hundred thirty-five patients (70 women, 65 men; median age, 59 years) with biopsy-proven tumors, liver metastases, and no autoimmune disease. Interventions: Leukocyte alpha-interferon (n = 88) or alpha-interferon 2b (n = 47) three times a week. Main Outcome Measures: Signs and symptoms of autoimmune disease or development of autoantibodies to thyroid antigens, nuclear antigens, or gastric parietal cells. Tumor responses were determined by reduced liver metastases or reduced urinary 5-hydroxyindole acetic acid excretion, or both. Results: Twenty-five patients (19%) developed the following autoimmune disorders after a median of 9 months of therapy: thyroid disease (n = 18), systemic lupus erythematosus (n = 1), pernicious anemia (n = 4), and vasculitis (n = 2). Antibodies to microsomal thyroid antigen or thyroglobulin were detected in 16 patients before therapy and in another 11 patients during therapy. Antinuclear antibodies were detected in 16 patients before and in another 19 patients during therapy. Clinical thyroid disease developed in more than 60% of patients who had or developed thyroid antibodies but in only 7% of initially autoantibody-negative patients. Autoimmunity did not correlate with objective tumor response. Conclusion: Patients with malignant carcinoid tumors may develop autoimmune disease during alpha-interferon therapy, especially when autoantibodies are present. They should therefore be monitored for autoimmunity, which does not appear, however, to influence tumor responses.