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.
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.
Karthaus
M
M
Med. Klinik II, Ev. Johannes-Krankenhaus, Bielefeld, Germany. Meinolf-Karthaus@Johanneswerk.de
Ballo
Harald
H
Abenhardt
Wolgang
W
Steinmetz
Tilmann
T
Geer
Thomas
T
Schimke
Jorg
J
Braumann
Dietrich
D
Behrens
Rudiger
R
Behringer
Dirk
D
Kindler
Manfred
M
Messmann
Helmut
H
Boeck
Hans-Peter
HP
Greinwald
Roland
R
Kleeberg
Ulrich
U
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
D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D059004:Topoisomerase I Inhibitors; D019819:Budesonide; D000077146:Irinotecan; D002166:Camptothecin