Ed. Dorval et al., EFFECT OF ENKEPHALINASE INHIBITION ON ACU TE CHEMOTHERAPY-INDUCED DIARRHEA IN MAN - RESULTS OF A PILOT-STUDY, Gastroenterologie clinique et biologique, 19(1), 1995, pp. 27-30
Background and objectives. - Acute chemotherapy induced diarrhoea may
require reducing or even stopping subsequent therapy. Antidiarrhoeal d
rug efficiency has not been extensively studied and the effects of the
new antisecretory compound acetorphan - a potent enkephalinase inhibi
tor active in acute diarrhoea - are unknown. The aim of this study was
to investigate the possible effects of acetorphan on 5 FU-induced dia
rrhoea in man. Material and methods. - Fifteen patients reporting acut
e diarrhoea following chemotherapy were included in this study. They p
resented with metastatic cole-rectal cancer (n = 14) or pancreatic car
cinoma (n = 1) and were treated once weekly, by an 8-hour IV infusion
of folinic acid 200 mg/m(2) and 5 FU 1,800 to 3,000 mg/m(2). In. each
patient, number and consistency of stools were assessed every day duri
ng 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 present
ed with diarrhoea (> 3 stools/day for > 2 days: WHO grades 2 and 3); w
ith 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 acetorpha
n, there was a close positive linear relationship between the percent
reduction in the number of stools and the number of stools during cont
rol period up to a 8 stools/day level (8 patients) above which efficie
ncy decreased (4 patients). Conclusion. - These results suggest the ef
ficacy of acetorphan on chemotherapy-induced diarrhoea and urgent need
for a randomized controlled trial.