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


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).


CONCLUSIONS
These results suggest the efficacy of acetorphan on chemotherapy-induced diarrhoea and urgent need for a randomized controlled trial.
Dorval
E D
ED
Service de Gastroentérologie, CHU, Tours.
Regimbeau
C
C
Gamelin
E
E
Picon
L
L
Bérard
H
H
D000208:Acute Disease; D000230:Adenocarcinoma / Q000188:drug therapy / Q000601:surgery; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000601:surgery; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015260:Neprilysin / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D011446:Prospective Studies; D015244:Thiorphan / Q000031:analogs & derivatives* / Q000627:therapeutic use
C049331:racecadotril; D015244:Thiorphan; D015260:Neprilysin; D005472:Fluorouracil
Traitement de la diarrhée aiguë chimio-induite par inhibition de l'enképhalinase. Résultats d'une étude pilote.