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

Vol. 68, No. 4-6, 2005

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Clinical Study

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
M. Karthaus^a, Harald Ballo^b, Wolgang Abenhardt^c, Tilmann Steinmetz^d, Thomas Geer^e, Jörg Schimke^f, Dietrich Braumann^g, Rüdiger Behrens^h, Dirk Behringerⁱ, Manfred Kindler^j, Helmut Messmann^k, Hans-Peter Boeck^b, Roland Greinwald^l, Ulrich Kleeberg^m

^aMed. Klinik II, Ev. Johannes-Krankenhaus, Bielefeld,
^bHämatologisch-Onkologische Praxis, Offenbach,
^cHämatologisch-Onkologische Praxis, München,
^dHämatologisch-Onkologische Praxis, Köln,
^eDiakonie Krankenhaus, Schwäbisch Hall,
^fHämatologisch-Onkologische Praxis, Saarbrücken,
^gAKH Altona, Hamburg,
^hOnkologische Praxis, Halle,
ⁱUniversitätsklinikum Freiburg,
^jOnkologische Praxis, Berlin,
^kKlinikum der Universität Regensburg,
^lDr. Falk Pharma GmbH, Freiburg, and
^mHämatologisch-Onkologische Praxis, Hamburg, Germany

Address of Corresponding Author

Oncology 2005;68:326-332 (DOI: 10.1159/000086971)

Key Words

Irinotecan diarrhea
Prophylaxis
Budesonide colorectal cancer

Abstract

Background: Unpredictable and severe diarrhea (NCI grade 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. Patients and 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). Conclusion: 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.

Author Contacts

Meinolf Karthaus
Med. Klinik II, Ev. Johannes-Krankenhaus
Schildescher Strasse 99, DE-33611 Bielefeld (Germany)
Tel. +49 521 8014304, Fax +49 521 8014307
E-Mail Meinolf-Karthaus@Johanneswerk.de

Article Information

The study was presented in part at the 39th ASCO meeting 2003, Chicago (oral presentation A 2935).

Received: July 21, 2004
Accepted after revision: October 3, 2004
Published online: July 12, 2005
Number of Print Pages : 7
Number of Figures : 0, Number of Tables : 5, Number of References : 25

Medline Abstract (ID 16020959)

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