Combination therapy with octreotide and alpha-interferon: effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors.

Abstract

We investigated the antiproliferative efficacy of the addition of alpha-interferon to the somatostatin analogue octreotide in patients with metastasized gastroenteropancreatic tumors unresponsive to octreotide monotherapy. In an open prospective trial, 21 patients with metastasized neuroendocrine gastroenteropancreatic tumors (nine patients with carcinoid syndrome, eight with nonfunctioning tumors, four with gastrinoma) were treated with 5 x 10(6) IU alpha-interferon tiw in addition to 200 microg of octreotide tid. All patients, including 16 patients with preceding monotherapy with 200 microg of octreotide tid, had tumor progression documented by computed tomography before entering the study. Growth response (computed tomography documented) and biochemical response were assessed at 3-month intervals. Inhibition of tumor growth was observed in 14 patients (67%), 11 of whom had preceding octreotide monotherapy; complete regression was observed in one patient lasting for 49 months and stable disease (stand-still) in 13 patients lasting for 3 to 52 months (median, 12 months). Seven patients failing this combination therapy exhibited a significantly shorter overall survival (median, 23 months; range, 5 to 42 months) than the 14 patients responding to this regimen (median, 68 months; range, 12 to 112 months; p = 0.007). Two patients are still alive. Biochemical response was achieved in 69% of patients with functioning tumors: in three of four patients with gastrinoma and in six of nine patients with carcinoid syndrome. These data suggest that the addition of alpha-interferon to octreotide has antiproliferative efficacy in a subgroup of patients with advanced metastatic disease unresponsive to octreotide monotherapy. Prolonged survival was seen in the responder group.