title: Effects of Budesonide on Cabazitaxel Pharmacokinetics and Cabazitaxel-Induced Diarrhea: A Randomized, Open-Label Multicenter Phase II Study.
abstract: Purpose:Forty-seven percent of patients in the pivotal trial of cabazitaxel reported diarrhea of any grade. Aiming to reduce the incidence of diarrhea, we studied the effects of budesonide on the grade of cabazitaxel-induced diarrhea during the first two treatment cycles.Experimental Design:Between December 2011 and October 2015, 246 metastatic castration-resistant prostate cancer patients were randomized to receive standard-of-care cabazitaxel 25 mg/m2every 3 weeks plus prednisone 10 mg/day (group CABA) or same dose/schedule of cabazitaxel with concomitant budesonide 9 mg daily during the first two treatment cycles (group BUD). The occurrence of diarrhea was reported by physicians and by patients in a diary. χ2tests were used to compare incidence numbers. An intention-to-treat principle was used.Results:In the phase II trial, 227 patients were evaluable. Grade 2-3 diarrhea occurred in 35 patients (15%) and grade 4 diarrhea was not reported. The incidence of grade 2-3 diarrhea was comparable in both treatment groups: 14 of 113 patients in group CABA (12%) versus 21 of 114 patients in group BUD (18%;P= 0.21). Seven patients were admitted to the hospital with diarrhea (n= 5 group CABA vs.n= 2 group BUD). PSA response was seen in 30% of patients and was not affected by budesonide coadministration (P= 0.29). Also, other toxicities were not affected by budesonide coadministration.Conclusions:The incidence of cabazitaxel-induced diarrhea was notably lower than reported in the TROPIC trial and appears manageable in routine clinical practice. Budesonide coadministration did not reduce the incidence or severity of cabazitaxel-induced diarrhea.Clin Cancer Res; 23(7); 1679-83. ©2016 AACR.
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
authors.forename: Annemieke J M
authors.initials: AJ
authors.lastname: Nieuweboer
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
authors.forename: Anne-Joy M
authors.initials: AM
authors.lastname: de Graan
authors.affiliation: Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Hamberg
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Bins
authors.affiliation: Department of Urology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: van Soest
authors.affiliation: Department of Internal Medicine, TweeSteden Ziekenhuis, Tilburg, the Netherlands.
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: van Alphen
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands.
authors.forename: Andries M
authors.initials: AM
authors.lastname: Bergman
authors.affiliation: Department of Internal Medicine, Spaarne Gasthuis, Hoofddorp, the Netherlands.
authors.forename: Aart
authors.initials: A
authors.lastname: Beeker
authors.affiliation: Department of Internal Medicine, Admiraal de Ruyter Ziekenhuis, Goes/Vlissingen, the Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: van Halteren
authors.affiliation: Department of Internal Medicine, Amphia Ziekenhuis, Breda, the Netherlands.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Ten Tije
authors.affiliation: Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Zuetenhorst
authors.affiliation: Clinical Trial Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
authors.forename: Nelly
authors.initials: N
authors.lastname: van der Meer
authors.affiliation: Clinical Trial Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
authors.forename: Dana
authors.initials: D
authors.lastname: Chitu
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: de Wit
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. a.mathijssen@erasmusmc.nl.
authors.forename: Ron H J
authors.initials: RH
authors.lastname: Mathijssen
mesh_terms: D000328:Adult; D000368:Aged; D019819:Budesonide / Q000008:administration & dosage*; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D064129:Prostatic Neoplasms, Castration-Resistant / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D019819:Budesonide; C552428:cabazitaxel