BACKGROUND: Carcinoid diarrhoea is associated with rapid small bowel and proximal colonic transit. Intravenous administration of a serotonin type 3 receptor (5HT3) antagonist restores postprandial colonic tone towards normal in carcinoid patients. AIMS: To evaluate the medium-term effects of an oral 5HT3 antagonist, alosetron, on symptoms, stool fat, and transit in patients with carcinoid diarrhoea. METHODS: In 27 patients with carcinoid diarrhoea, symptoms were recordeddaily and gastrointestinal transit was measured by scintigraphy in a three dose (0.1, 0.5, 2.0 mg, twice daily), randomised (1:1:1), parallel group, four week study. Placebo was given during the first week. Loperamide (2 mg capsules) was used as rescue medication. RESULTS: There were numerical improvements in median diarrhoea score, stool weight, loperamide use, and overall colonic transit at four hours, but no overall significant drug effect was shown. Alosetron reduced the proximal colon emptying rate (p < 0.05 in 20 evaluable comparisons), but did not significantly alter small bowel transit. CONCLUSIONS:Alosetron retardation of proximal colonic emptying in patients with carcinoid diarrhoea confirms the potential role of a 5HT3 mechanism in this disorder. Doses of alosetron higher than 2.0 mg twice daily will be required for symptomatic benefit in carcinoid diarrhoea.
RCT Entities:
BACKGROUND:Carcinoid diarrhoea is associated with rapid small bowel and proximal colonic transit. Intravenous administration of a serotonin type 3 receptor (5HT3) antagonist restores postprandial colonic tone towards normal in carcinoidpatients. AIMS: To evaluate the medium-term effects of an oral 5HT3 antagonist, alosetron, on symptoms, stool fat, and transit in patients with carcinoid diarrhoea. METHODS: In 27 patients with carcinoid diarrhoea, symptoms were recorded daily and gastrointestinal transit was measured by scintigraphy in a three dose (0.1, 0.5, 2.0 mg, twice daily), randomised (1:1:1), parallel group, four week study. Placebo was given during the first week. Loperamide (2 mg capsules) was used as rescue medication. RESULTS: There were numerical improvements in median diarrhoea score, stool weight, loperamide use, and overall colonic transit at four hours, but no overall significant drug effect was shown. Alosetron reduced the proximal colon emptying rate (p < 0.05 in 20 evaluable comparisons), but did not significantly alter small bowel transit. CONCLUSIONS:Alosetronretardation of proximal colonic emptying in patients with carcinoid diarrhoea confirms the potential role of a 5HT3 mechanism in this disorder. Doses of alosetron higher than 2.0 mg twice daily will be required for symptomatic benefit in carcinoid diarrhoea.
Authors: N J Talley; S F Phillips; A Haddad; L J Miller; C Twomey; A R Zinsmeister; R L MacCarty; A Ciociola Journal: Dig Dis Sci Date: 1990-04 Impact factor: 3.199
Authors: G Stacher; U Weber; G Stacher-Janotta; P Bauer; K Huber; A Holzäpfel; G Krause; C Steinborn Journal: Br J Clin Pharmacol Date: 2000-05 Impact factor: 4.335
Authors: A E Bharucha; M Camilleri; S Haydock; I Ferber; D Burton; S Cooper; D Tompson; K Fitzpatrick; R Higgins; A R Zinsmeister Journal: Gut Date: 2000-11 Impact factor: 23.059
Authors: Reto M Kaderli; Marko Spanjol; Attila Kollár; Lukas Bütikofer; Viktoria Gloy; Rebecca A Dumont; Christian A Seiler; Emanuel R Christ; Piotr Radojewski; Matthias Briel; Martin A Walter Journal: JAMA Oncol Date: 2019-04-01 Impact factor: 31.777