Maeda Akimitsu, Matsuo Keitaro, Ando Hitoshi, Morishige Jun-Ichi, Muro Kei, Uchida Kosaku, Tajika Masahiro
Department of Pharmacy, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.
Division of Cancer Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Aichi, Japan.
Br J Clin Pharmacol. 2025 Apr;91(4):1216-1222. doi: 10.1111/bcp.16359. Epub 2024 Dec 2.
Paclitaxel and nanoparticle albumin-bound (nab)-paclitaxel can cause early, extremely severe neutropenia, occasionally leading to fatal outcomes. As paclitaxel is a substrate of P-glycoprotein, this study aimed to investigate the impact of ABCB1 single-nucleotide variants, which encode P-glycoprotein, on early, extremely severe neutropenia in patients receiving paclitaxel/nab-paclitaxel plus ramucirumab as second-line therapy for unresectable advanced/recurrent gastric cancer.
We analysed patients treated at Aichi Cancer Center Hospital from January 2018 to August 2023, with DNA samples stored in the Cancer BioBank Aichi. The impact of ABCB1 variants T1236C (rs1128503), G2677T/A (rs2032582) and C3435T (rs1045642) on early, extremely severe neutropenia was examined. Neutropenia was defined as a decline in neutrophil count to <100/μL within 28 days of therapy initiation. Firth's logistic regression evaluated the association between the ABCB1 C3435T (rs1045642) TT genotype and early, extremely severe neutropenia, adjusted for age, sex, baseline neutrophil count, and serum albumin and aspartate aminotransferase levels.
Of the 203 eligible patients, 5 (2%) experienced neutropenia with neutrophil counts of <100/μL. The odds ratio for neutrophil counts of <100/μL was 28.1 (95% confidence interval 2.8-283.3) in patients with the ABCB1 C3435T (rs1045642) TT genotype.
The ABCB1 C3435T (rs1045642) TT genotype was significantly associated with early, extremely severe neutropenia in patients receiving paclitaxel/nab-paclitaxel. Evaluating this genotype status may help predict those at increased risk for early, extremely severe neutropenia.
紫杉醇和纳米白蛋白结合型（nab）紫杉醇可导致早期极为严重的中性粒细胞减少症，偶尔会导致致命后果。由于紫杉醇是P-糖蛋白的底物，本研究旨在探讨编码P-糖蛋白的ABCB1单核苷酸变异对接受紫杉醇/nab-紫杉醇联合雷莫西尤单抗作为不可切除的晚期/复发性胃癌二线治疗的患者早期极为严重的中性粒细胞减少症的影响。
我们分析了2018年1月至2023年8月在爱知癌症中心医院接受治疗的患者，其DNA样本存储在爱知癌症生物库中。研究了ABCB1变异T1236C（rs1128503）、G2677T/A（rs2032582）和C3435T（rs1045642）对早期极为严重的中性粒细胞减少症的影响。中性粒细胞减少症定义为治疗开始后28天内中性粒细胞计数降至<100/μL。Firth逻辑回归评估了ABCB1 C3435T（rs1045642）TT基因型与早期极为严重的中性粒细胞减少症之间的关联，并对年龄、性别、基线中性粒细胞计数以及血清白蛋白和天冬氨酸转氨酶水平进行了校正。
在203名符合条件的患者中，5名（2%）出现中性粒细胞减少症，中性粒细胞计数<100/μL。ABCB1 C3435T（rs1045642）TT基因型患者中性粒细胞计数<100/μL的比值比为28.1（95%置信区间2.8 - 283.3）。
ABCB1 C3435T（rs1045642）TT基因型与接受紫杉醇/nab-紫杉醇治疗的患者早期极为严重的中性粒细胞减少症显著相关。评估该基因型状态可能有助于预测早期极为严重的中性粒细胞减少症风险增加的患者。
