Medium-term effects of a new 5HT3 antagonist, alosetron, in patients with carcinoid diarrhoea

Abstract

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 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: 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.

Figure 1

Cumulative use of rescue medication (loperamide) during the active treatment portion of the trial.

Figure 2

Dose related effects of alosetron on small bowel transit time (A), proximal colonic emptying (t_1/2) (B), and geometric centre at four hours (C) in patients with carcinoid diarrhoea.