TY - JOUR
T1 - Effects of Budesonide on Cabazitaxel Pharmacokinetics and Cabazitaxel-Induced Diarrhea
T2 - A Randomized, Open-Label Multicenter Phase II Study
AU - Dutch Uro-Oncology Studygroup (DUOS)
AU - Nieuweboer, Annemieke J M
AU - de Graan, Anne-Joy M
AU - Hamberg, Paul
AU - Bins, Sander
AU - van Soest, Robert J
AU - van Alphen, Robbert J
AU - Bergman, Andries M
AU - Beeker, Aart
AU - van Halteren, Henk
AU - Ten Tije, Albert J
AU - Zuetenhorst, Hanneke
AU - van der Meer, Nelly
AU - Chitu, Dana
AU - de Wit, Ronald
AU - Mathijssen, Ron H J
N1 - ©2016 American Association for Cancer Research.
PY - 2017/4/2
Y1 - 2017/4/2
N2 - 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/m2 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. χ2 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.
AB - 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/m2 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. χ2 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.
U2 - 10.1158/1078-0432.ccr-16-2110
DO - 10.1158/1078-0432.ccr-16-2110
M3 - Article
C2 - 27702823
SN - 1078-0432
VL - 23
SP - 1679
EP - 1683
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 7
ER -