[Treatment of acute chemically induced diarrhea by inhibition of enkephalinase. Results of a pilot study].

Abstract

BACKGROUND AND OBJECTIVES:

Acute chemotherapy-induced diarrhoea may require reducing or even stopping subsequent therapy. Antidiarrhoeal drug efficiency has not been extensively studied and the effects of the new antisecretory compound acetorphan--a potent enkephalinase inhibitor active in acute diarrhoea--are unknown. The aim of this study was to investigate the possible effects of acetorphan on 5 FU-induced diarrhoea in man.

MATERIAL AND METHODS:

Fifteen patients reporting acute diarrhoea following chemotherapy were included in this study. They presented with metastatic colo-rectal cancer (n = 14) or pancreatic carcinoma (n = 1) and were treated, once weekly, by an 8-hour IV infusion of folinic acid 200 mg/m2 and 5 FU 1,800 to 3,000 mg/m2. In each patient, number and consistency of stools were assessed every day during the week following chemotherapy, once without (control period) and once with acetorphan p.o. 300 mg/d/7d.

RESULTS:

During the control period, 3 out of 15 patients did not have significant diarrhoea, but 2 out of 3 patients had abdominal pain which was relieved by acetorphan without appearance of constipation. Twelve out of 15 patients presented with diarrhoea (> 3 stools/day for > 2 days: WHO grades 2 and 3); with acetorphan, the number of stools per day was reduced in all cases from 6.3 (range: 3-10.6) to 4.9 (range: 2.6-8.9) (P < 0.002), and the number of days with liquid stools dropped from 4.7 (range: 2-7) to 2.4 (range: 0-7) (P < 0.02). In addition, during treatment with acetorphan, there was a close positive linear relationship between the percent reduction in the number of stools and the number of stools during control period up to a 8 stools/day level (8 patients) above which efficiency decreased (4 patients).

CONCLUSION:

These results suggest the efficacy of acetorphan on chemotherapy-induced diarrhoea and urgent need for a randomized controlled trial.

• Authors: E D Dorval, C Regimbeau, E Gamelin, L Picon, H Bérard
• Journal: Gastroenterologie clinique et biologique (Gastroenterol Clin Biol) Vol. 19 Issue 1 Pg. 27-30 (Jan 1995) ISSN: 0399-8320 [Print] France
• Vernacular Title: Traitement de la diarrhée aiguë chimio-induite par inhibition de l'enképhalinase. Résultats d'une étude pilote.
• PMID: 7720986 (Publication Type: Clinical Trial, English Abstract, Journal Article)

Chemical References

• racecadotril
• Thiorphan
• Neprilysin
• Fluorouracil

Topics

• Acute Disease
• Adenocarcinoma (drug therapy, surgery)
• Adult
• Aged
• Colorectal Neoplasms (drug therapy, surgery)
• Combined Modality Therapy
• Diarrhea (chemically induced, drug therapy)
• Female
• Fluorouracil (adverse effects, therapeutic use)
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis
• Neprilysin (antagonists & inhibitors, therapeutic use)
• Prospective Studies
• Thiorphan (analogs & derivatives, therapeutic use)