CLINICAL EFFICACY OF OCTREOTIDE IN THE TREATMENT OF METASTATIC NEUROENDOCRINE TUMORS - A STUDY BY THE ITALIAN TRIALS IN MEDICAL ONCOLOGY GROUP

BACKGROUND. The unsatisfactory control of neuroendocrine tumor growth with chemotherapy and/or interferon (IFN-2a) stimulated us to investig ate the role of the somatostatin analogue octreotide (SMS 201.995), wh ich is reported to be highly effective on controlling carcinoid syndro me symptoms. Octreotide has been used in a wide range of doses, and it was postulated that higher doses might lead to an objective response. METHODS, The aim of the present multicenter Phase II study was to det ermine the safety and efficacy of SMS 201.995 in controlling carcinoid s and other neuroendocrine tumors. Fifty-eight patients were treated s ubcutaneously with 2 sequential doses of the drug (Sandostatina(R), Sa ndoz, Inc., S,b.A. Pharmaceuticals, Basel, Switzerland). The first 23 patients received 500 mu g 3 times a day and the remaining 35 patients received 1000 mu g 3 times a day. The treatment was continued until t he tumor progressed. RESULTS. All of the patients were adequately trea ted and evaluated. The predominant histotype was carcinoid, although t here were instances of medullary thyroid carcinoma, pancreatic islet c ell tumors, and Merkel cell carcinoma. Carcinoid syn drome was documen ted in 16 patients and abnormal urinary 5-hydroxyindoloacetic acid exc retion in 15. The median treatment duration was 5 months (range, 2-31 months). The responses were evaluated in three categories: tumor regre ssion for tumor growth control, symptom response, and biochemical resp onse. There was an effect on tumor growth in two patients with carcino ids. Symptomatic control was achieved in 73% of patients and a biochem ical response in 77% of patients. In twenty-seven patients, the diseas e stabilized for at least 6 months (range, 6-32+). The median survival time for all patients was 22 months (range, 1-32+). CONCLUSIONS, In t erms of tumor regression, octreotide is disappointing (partial respons e: 3%); symptomatic response and biochemical control are satisfactory. These data confirm that somatostatin analogues are comparable to inte rferons in the treatment of carcinoid syndrome, although other efforts are necessary to control tumor regression. (C) 1996 American Cancer S ociety.