title: Prospective, double-blind, placebo-controlled, multicenter, randomized phase III study with orally administered budesonide for prevention of irinotecan (CPT-11)-induced diarrhea in patients with advanced colorectal cancer.
abstract: BACKGROUND
  Unpredictable and severe diarrhea (NCI grade > or =3) remains a life-threatening adverse event in patients treated with irinotecan (CPT-11). The aim of this study was to evaluate the efficacy and safety of orally administered budesonide for prevention of CPT-11-induced delayed diarrhea in patients with advanced colorectal cancer.
  
  
  METHODS
  A total of 56 patients with advanced colorectal cancer receiving CPT-11 therapy (125 mg/m2 once weekly) were enrolled in this multicenter trial. Patients were randomly treated with 3 mg budesonide orally 3 times daily versus placebo. Detailed assessment of diarrhea by monitoring stool frequency, stool consistency and loperamide rescue medication was made by keeping a diary.
  
  
  RESULTS
  Diarrhea, defined as number of stools >4 occurring on a single day during the study period, could be prevented in 58.3% of the budesonide-treated patients compared to 38.5% of the patients under placebo. Patients in the budesonide group had less episodes (0.7 vs. 2.2 episodes) and a considerably shorter total duration of diarrhea (1.8 vs. 4.2 days) episodes than patients in the placebo group. Loperamide use was more frequent in the placebo than in the budesonide arm (55.6 vs. 41.7%). Also, exposure to rescue medication of loperamide was higher for placebo (36.2 capsules) than for budesonide (24.9 capsules). A superior prevention of diarrhea was observed for budesonide compared to placebo in the first cycle (14 vs. 10; p = 0.257), with more failures observed in the placebo group (16 vs. 10).
  
  
  CONCLUSIONS
  This double-blind randomized trial failed to show that budesonide has a significant benefit in preventing CPT-11-induced diarrhea. While a trend exists, further trials are warranted.
authors: Med. Klinik II, Ev. Johannes-Krankenhaus, Bielefeld, Germany. Meinolf-Karthaus@Johanneswerk.de
authors: M
authors: M
authors: Karthaus
authors: Harald
authors: H
authors: Ballo
authors: Wolgang
authors: W
authors: Abenhardt
authors: Tilmann
authors: T
authors: Steinmetz
authors: Thomas
authors: T
authors: Geer
authors: Jorg
authors: J
authors: Schimke
authors: Dietrich
authors: D
authors: Braumann
authors: Rudiger
authors: R
authors: Behrens
authors: Dirk
authors: D
authors: Behringer
authors: Manfred
authors: M
authors: Kindler
authors: Helmut
authors: H
authors: Messmann
authors: Hans-Peter
authors: HP
authors: Boeck
authors: Roland
authors: R
authors: Greinwald
authors: Ulrich
authors: U
authors: Kleeberg
mesh_terms: D000284:Administration, Oral; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D019819:Budesonide / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D059004:Topoisomerase I Inhibitors; D019819:Budesonide; D000077146:Irinotecan; D002166:Camptothecin