2-met-4-(4-nitro)-phe-5-pronh2-enkephalin and Diarrhea

Diarrhea commonly occurs following the administration of cisplatin. BW942C, a pentapeptide, is a synthetic enkephalin shown to control castor oil-induced and traveler's diarrhea. To assess the safety and efficacy of BW942C in controlling diarrhea caused by cisplatin, 30 adults with lung cancer who had already experienced diarrhea (three or more loose bowel movements) during the 24-hour period following a prior cisplatin administration were randomized to receive either BW942C or placebo during the next cisplatin course. All patients received a concomitant antiemetic regimen including metoclopramide, dexamethasone, and lorazepam during all courses. Patients administered BW942C experienced less diarrhea (27% v 67%, P = .02). Twenty-seven percent of patients given the pentapeptide had loose bowel movements as opposed to 93% who received placebo (P = .0002). There were no significant differences in the incidence and degree of vomiting and other treatment-related side effects observed between the placebo and treatment groups. We conclude that oral BW942C is more effective than placebo in controlling diarrhea following cisplatin chemotherapy.

Topics: Adult; Antidiarrheals; Cisplatin; Clinical Trials as Topic; Diarrhea; Double-Blind Method; Enkephalin, Methionine; Enkephalins; Female; Humans; Male; Middle Aged; Neoplasms; Placebos; Random Allocation

The efficacy of BW942C, a novel enkephalinlike pentapeptide antidiarrheal agent, was compared with the efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) and the combination of the two agents in a placebo-controlled trial of the 72-h treatment of acute diarrhea. Subjects with diarrhea but without bloody stools or fever greater than 102 degrees F (38.9 degrees C) were enrolled. Administered to 134 U.S. adults with diarrhea that developed shortly after their arrival in Guadalajara, Mexico, BW942C was more efficacious than TMP-SMX in relieving diarrhea and cramps in the first 12 h of therapy, especially among subjects with diarrhea caused by enterotoxigenic E. coli. In the BW942C treatment group, 25% of subjects eventually took additional therapy because their diarrhea did not respond to BW942C alone. Neurological side effects such as dizziness and light-headedness occurred more frequently among BW942C-treated subjects. Therapy for 3 days with TMP-SMX provided lasting relief comparable with previously reported 5-day therapy. Use of the combination of both agents provided the benefits of prompt relief afforded by BW942C and lasting relief afforded by TMP-SMX. BW942C might prove to be an agent suitable for the treatment of acute diarrhea, with TMP-SMX reserved for treatment of those who do not respond adequately. The empiric use of the combination of BW942C and TMP-SMX appears appropriate for the treatment of severe nondysenteric disease.

Topics: Antidiarrheals; Clinical Trials as Topic; Diarrhea; Double-Blind Method; Drug Combinations; Enkephalin, Methionine; Enkephalins; Feces; Female; Humans; Male; Mexico; Random Allocation; Sulfamethoxazole; Travel; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; United States