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 multicenterphase II study

Delayed diarrhea is the main toxicity of irinotecan at the currently recomm ended dose of 350 mg/m(2) 30-minute intravenous infusion, once every 3 week s. This phase II, multicenter, open-label, randomized study was primarily d esigned 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 irinote can. The patients were randomly allocated either to group A (68 patients) a nd received Tiorfan (300 mg/day) from DO to D15 or to group B (68 patients) with no prophylactic treatment. Delayed diarrhea occurred in 197 of 355 cy cles (558) 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 3 1 of 68 evaluable patients (45%) in group B. No difference was observed bet ween the two groups for delayed diarrhea characteristics, incidence, or sev erity. The response rate in 99 evaluable patients was 12.1% (6.4%-20.2%). T his study has shown that Tiorfan given prophylactically at 300 mg/day has n o effect on delayed diarrhea.