Fujimoto Yuki, Ueno Shikiko, Oda Kazutaka, Gunda Nao, Shimomura Yumi, Nishimura Yuka, Yamaguchi Ayami, Kuwano Akari, Ito Yuki, Baba Yusuke, Nishigaki Aina, Michiwaki Natsumi, Uchino Shota, Kurogi Kayo, Kawano Yawara, Matsuoka Masao, Saito Hideyuki, Okuno Yutaka, Jono Hirofumi
Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Department of Pharmacy, National Hospital Organization Beppu Medical Center, Beppu 874-0011, Japan.
Cancers (Basel). 2021 Nov 12;13(22):5674. doi: 10.3390/cancers13225674.
(1) Background: multiple myeloma patients have benefited from bortezomib therapy, though it has often been discontinued owing to diarrhea. The objective of this study was to verify serum bortezomib concentration in the emergence of diarrhea. (2) Methods: this prospective, observational case-control, and monocentric study was performed with an approval by the Ethics Committee of Kumamoto University Hospital in 2015 (No. 1121) from February 2015 to April 2017. (3) Results: twenty-four patients with bortezomib therapy were recruited; eight patients (33.3%) developed diarrhea at day 3 as median. Median measured trough bortezomib concentration at 24 h after first or second dose for patients with or without diarrhea was 0.87 or 0.48 ng/mL, respectively ( 0.04, Wilcoxon signed rank test). Receiver operation characteristic (ROC) analysis produced the cut-off concentration of 0.857 ng/mL (area under the ROC curve of 0.797, sensitivity of 0.625, specificity of 0.875). The survival curves between patients with and without diarrhea were similar ( 0.667); those between patients with higher and lower concentration than median value (0.61 ng/mL) were also similar ( 0.940). (4) Conclusions: this study indicated the possible involvement of serum bortezomib concentration in the emergence of diarrhea in bortezomib therapy in patients with multiple myeloma.
(1) 背景：尽管硼替佐米治疗常因腹泻而中断，但多发性骨髓瘤患者已从中受益。本研究的目的是验证腹泻出现时血清硼替佐米的浓度。(2) 方法：本前瞻性、观察性病例对照单中心研究于2015年2月至2017年4月在熊本大学医院伦理委员会批准下进行（编号1121）。(3) 结果：招募了24例接受硼替佐米治疗的患者；8例患者（33.3%）在第3天出现腹泻，中位数为第3天。有腹泻和无腹泻患者在首次或第二次给药后24小时测量的硼替佐米谷浓度中位数分别为0.87或0.48 ng/mL（P = 0.04，Wilcoxon符号秩检验）。受试者工作特征（ROC）分析得出临界浓度为0.857 ng/mL（ROC曲线下面积为0.797，灵敏度为0.625，特异性为0.875）。有腹泻和无腹泻患者的生存曲线相似（P = 0.667）；硼替佐米浓度高于和低于中位数（0.61 ng/mL）的患者生存曲线也相似（P = 0.940）。(4) 结论：本研究表明血清硼替佐米浓度可能与多发性骨髓瘤患者硼替佐米治疗中腹泻的出现有关。
