Background: The unsatisfactory control of neuroendocrine tumor growth with chemotherapy and/or interferon (IFN-2a) stimulated us to investigate the role of the somatostatin analogue octreotide (SMS 201.995), which is reported to be highly effective in controlling carcinoid syndrome 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 determine the safety and efficacy of SMS 201.995 in controlling carcinoids and other neuroendocrine tumors. Fifty-eight patients were treated subcutaneously with 2 sequential doses of the drug (Sandostatina, Sandoz, Inc., S.b.A. Pharmaceuticals, Basel, Switzerland). The first 23 patients received 500 micrograms 3 times a day and the remaining 35 patients received 1000 micrograms 3 times a day. The treatment was continued until the tumor progressed.
Results: All of the patients were adequately treated and evaluated. The predominant histotype was carcinoid, although there were instances of medullary thyroid carcinoma, pancreatic islet cell tumors, and Merkel cell carcinoma. Carcinoid syndrome was documented in 16 patients and abnormal urinary 5-hydroxyindoloacetic acid excretion in 15. The median treatment duration was 5 months (range, 2-31 months). The responses were evaluated in three categories: tumor regression for tumor growth control, symptom response, and biochemical response. There was an effect on tumor growth in two patients with carcinoids. Symptomatic control was achieved in 73% of patients and a biochemical response in 77% of patients. In twenty-seven patients, the disease stabilized for at least 6 months (range, 6-32+). The median survival time for all patients was 22 months (range, 1-32+).
Conclusions: In terms of tumor regression, octreotide is disappointing (partial response: 3%); symptomatic response and biochemical control are satisfactory. These data confirm that somatostatin analogues are comparable to interferons in the treatment of carcinoid syndrome, although other efforts are necessary to control tumor regression.