Study of Glutamine as Prophylaxis for Irinotecan Induced Diarrhea
Status:
Completed
Trial end date:
2010-01-01
Target enrollment:
Participant gender:
Summary
Irinotecan (7-ethyl-10- {4(-1-piperidino)-1-piperidino} carbonyloxy camptothecin) is a
semisynthetic camptothecin derivative introduced in the 1980's. Irinotecan is a prodrug
metabolized by carboxylesterases to an active metabolite 7-ethyl-10-hydroxy-camptothecin
(SN38). SN38 exerts its cytotoxic effect by forming stable complexes with topoisomerase I and
DNA. These complexes collide with replication forks and cause breaks in DNA. Studies
substantiated irinotecan's activity in 5FU resistant colorectal cancer and led to its
approval for treatment of 5FU resistant colorectal cancer in the United States, Canada and
Europe.Colorectal cancer studies demonstrated that single agent irinotecan's dose limiting
toxicity was diarrhea occurring 5 to 6 days after its administration. High dose loperamide at
first occurrence of diarrhea has decreased the incidence of diarrhea but the incidence of
grade 3/4 diarrhea remains high at 28 to 40%.