727 A phase II study of CPT 11 (irinotecan) in refractory to 5 FU colorectal cancer (CRC) with, preventive treatment of delayed diarrhea by acetorphan

According to Phase I data, Acetorphan a new anti-secretory anti-diarrheal agent might reduce the incidence and severity of CPT II induced diarrhea. In an attempt to confirm these results, an open randomized study has been performed, using this specific enkephalinase-inhibitor: Acetorphan (A). All patients (pts) had advanced CRC refractory to 5 FU and were treated with CPT 11 at the dose of 350 mg/m 2 every 3 weeks. In this study, the role of prophylactic A, 100 mg × 3/d has been randomly assessed versus no prophylaxis. Eighty eight pts have been so far entered and 45 are evaluable. Preliminary results suggest no difference in term of incidence or severity of D, but a trend towards a shorter duration and later occurrence of D in cycle 1 (3 versus 4.5 days and day 6 versus day 5 respectively) in patients receiving A and surprisingly a decrease in the incidence of grade 3 + 4 (OMS) neutropenia and febrile neutropenia. Conclusion The new anti-diarrheal agent A, may be of interest in the prophylactically management of CPT 11 induced diarrhea. Final results of these studies will be presented.