TREATMENT OF METASTATIC CARCINOIDS AND OTHER NEUROENDOCRINE TUMORS WITH RECOMBINANT INTERFERON-ALPHA-2A - A STUDY BY THE ITALIAN TRIALS IN MEDICAL ONCOLOGY GROUP

Background. Using a wide range of interferon (IFN) doses and schedules , a number of authors have found them to be active against neuroendocr ine tumors. Methods. To verify the clinical activity of IFN, 49 evalua ble patients with advanced stage low- and intermediate-grade neuroendo crine tumors were treated with recombinant IFN-alpha-2a at a daily dos e of 6 X 10(6) IU intramuscularly for 8 weeks, and 3 times weekly ther eafter. The predominant histotype was carcinoid, although a few cases had malignant islet cell tumors, medullary thyroid carcinoma, Merkel c ell carcinoma, or other neuroendocrine tumors. All of the patients had measurable lesions and most had multiple sites. Carcinoid syndrome wa s present in 14 cases. Results. After a median treatment duration of 6 months, complete regression was achieved in 1 of the 7 cases of medul lary thyroid carcinoma, and partial response was observed in 4 of 34 c arcinoids. Response duration ranged from 1-11 months. Control of the s yndrome was obtained in nine patients and a greater than or equal to 5 0% reduction of 5-hydroxyindoleacetic acid in eight patients. The trea tment was well-tolerated. The most frequently observed side effects we re fever, flu-like syndrome, and leukopenia. After 12 months of recomb inant IFN-alpha-2a, 15 cases in progression and 4 with stable disease or partial response received another treatment (either radiometabolic therapy with I-131 metaiodobenzylguanidine or polychemotherapy with st reptozotocin plus epirubicin). Conclusions. The use of recombinant IFN -alpha-2a at these doses is well-tolerated and effective in controllin g carcinoid syndrome (complete remission plus partial remission, 64%), although it has limited activity on tumor growth inhibition. No defin itive data can be given for the other protocol treatments.