EFFECT OF ENKEPHALINASE INHIBITION ON ACUTE CHEMOTHERAPY-INDUCED DIARRHEA IN MAN - RESULTS OF A PILOT-STUDY

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 cole-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/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 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.