Effects of Budesonide on Cabazitaxel Pharmacokinetics and Cabazitaxel-Induced Diarrhea: A Randomized, Open-Label Multicenter Phase II Study.

Autor:	Nieuweboer AJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., de Graan AM; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Hamberg P; Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands., Bins S; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., van Soest RJ; Department of Urology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., van Alphen RJ; Department of Internal Medicine, TweeSteden Ziekenhuis, Tilburg, the Netherlands., Bergman AM; Department of Medical Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands., Beeker A; Department of Internal Medicine, Spaarne Gasthuis, Hoofddorp, the Netherlands., van Halteren H; Department of Internal Medicine, Admiraal de Ruyter Ziekenhuis, Goes/Vlissingen, the Netherlands., Ten Tije AJ; Department of Internal Medicine, Amphia Ziekenhuis, Breda, the Netherlands., Zuetenhorst H; Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, the Netherlands., van der Meer N; Clinical Trial Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Chitu D; Clinical Trial Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., de Wit R; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Mathijssen RH; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. a.mathijssen@erasmusmc.nl.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2017 Apr 01; Vol. 23 (7), pp. 1679-1683. Date of Electronic Publication: 2016 Oct 04.
DOI:	10.1158/1078-0432.CCR-16-2110
Abstrakt:	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/m 2 every 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. χ 2 tests 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 . (©2016 American Association for Cancer Research.)
Databáze:	MEDLINE
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