title: Randomized comparison of prophylactic antidiarrheal treatment versus no prophylactic antidiarrheal treatment in patients receiving CPT-11 (irinotecan) for advanced 5-FU-resistant colorectal cancer: an open-label multicenter phase II study.
abstract: Delayed diarrhea is the main toxicity of irinotecan at the currently recommended dose of 350 mg/m2 30-minute intravenous infusion, once every 3 weeks. This phase II, multicenter, open-label, randomized study was primarily designed to evaluate the effect of a 15-day Tiorfan (racecadotril) treatment on the incidence and severity of irinotecan-induced delayed diarrhea. One hundred thirty-six patients with metastatic colorectal cancer who failed to respond to a 5-fluorouracil-based treatment received 714 cycles of irinotecan. The patients were randomly allocated either to group A (68 patients) and received Tiorfan (300 mg/day) from D0 to D15 or to group B (68 patients) with no prophylactic treatment. Delayed diarrhea occurred in 197 of 355 cycles (55%) in Group A and 203 of 344 cycles (59%) in Group B. grade III-IV diarrhea was reported in 17 of 40 compliant patients (42%) in group A and 31 of 68 evaluable patients (45%) in group B. No difference was observed between the two groups for delayed diarrhea characteristics, incidence, or severity. The response rate in 99 evaluable patients was 12.1% (6.4%-20.2%). This study has shown that Tiorfan given prophylactically at 300 mg/day has no effect on delayed diarrhea.
authors.affiliation: CRLC Val d'Aurelle, Montpellier, France.
authors.forename: M
authors.initials: M
authors.lastname: Ychou
authors.forename: J Y
authors.initials: JY
authors.lastname: Douillard
authors.forename: P
authors.initials: P
authors.lastname: Rougier
authors.forename: A
authors.initials: A
authors.lastname: Adenis
authors.forename: M
authors.initials: M
authors.lastname: Mousseau
authors.forename: P
authors.initials: P
authors.lastname: Dufour
authors.forename: J L
authors.initials: JL
authors.lastname: Wendling
authors.forename: F
authors.initials: F
authors.lastname: Burki
authors.forename: D
authors.initials: D
authors.lastname: Mignard
authors.forename: M
authors.initials: M
authors.lastname: Marty
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced* / Q000517:prevention & control*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin