Observations on the effect of a somatostatin analog in the Zollinger-Ellison syndrome: implications for the treatment of apudomas.
Somatostatin is known to inhibit hormone release and gastrointestinal secretion and hence may be useful in the treatment of amine precursor uptake, decarboxylase tumors. Clinical application has been limited by the short half-life, potency, and specificity of the natural hormone. Our study evaluated the effect of a synthetic analog of somatostatin, SMS 201-995 (Sandoz, Inc., E. Hanover, N.J.) on basal and stimulated gastrin release and gastric acid secretion in 10 patients with the Zollinger-Ellison syndrome. In experiment 1, H2-receptor antagonists were discontinued for 48 hours; SMS 201-995, 1 microgram/kg, was given subcutaneously; gastrin and SMS levels in plasma were determined by radioimmunoassay; and gastric secretion was measured and titrated at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, and 18 hours. The mean +/- SEM baseline gastrin level (1526 +/- 733 pg/ml) was significantly inhibited for 16 hours (p less than 0.05, paired t test). Gastric secretion was neutralized for as long as 18 hours (p 0.05). In experiment 2, three patients received either a secretin (2 U/kg) or a calcium stimulation test (2 mg/kg) with or without pretreatment with SMS 201-995, 1 microgram/kg, subcutaneously. The mean +/- SEM interpreted change in gastrin (ng X 60 min/ml) without SMS 201-995, 36.8 +/- 11 (secretin), and 129 +/- 30 (calcium) were reduced with SMS 201-995 to -1.1 +/- 0.76 (secretin) and -29 +/- 28 (calcium) (p less than 0.05). In the Zollinger-Ellison syndrome, SMS 201-995 caused significant and long-lasting inhibition of both tumor gastrin release and gastric acid secretion, probably by direct action on both the gastrinoma and the stomach. SMS 201-995 blocks acid secretion and secretin- and calcium-stimulated gastrin release, indicating that SMS 201-995 inhibits peptide secretion by postreceptor mechanisms. SMS 201-995 will be useful in the palliative treatment of apudomas.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001079:Apudoma / Q000188:drug therapy*; D002118:Calcium; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015282:Octreotide; D010166:Palliative Care; D011957:Receptors, Opioid; D012633:Secretin; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013268:Stimulation, Chemical; D013997:Time Factors; D015043:Zollinger-Ellison Syndrome / Q000188:drug therapy* / Q000378:metabolism
D000970:Antineoplastic Agents; D005755:Gastrins; D011957:Receptors, Opioid; D012633:Secretin; D013004:Somatostatin; D015282:Octreotide; D002118:Calcium