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肾功能损害作为三氟尿苷/胸苷磷酸化酶抑制剂联合贝伐单抗治疗中化疗引起的中性粒细胞减少的一个危险因素。

Renal impairment as a risk factor for chemotherapy induced neutropenia in the treatment of trifluridine/thymidine phosphorylase inhibitor plus bevacizumab.

作者信息

Shibutani Masatsune, Tanda Hideki, Kasashima Hiroaki, Fukuoka Tatsunari, Kashiwagi Shinichiro, Maeda Kiyoshi

机构信息

Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahi-machi Abeno-ku, Osaka City, 545-8585, Osaka Prefecture, Japan.

Department of Breast Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.

出版信息

Sci Rep. 2025 Jan 2;15(1):553. doi: 10.1038/s41598-024-84133-5.

Abstract

Although the phase III SUNLIGHT trial has demonstrated the survival benefit of the addition of bevacizumab (Bmab) to trifluridine/thymidine phosphorylase inhibitor (FTD/TPI), neutropenia, which frequently occurs during FDT/TPI + Bmab therapy, is a concern for clinicians. As TPI is excreted by the kidneys, the risk of adverse events is likely to be high in patients with an impaired renal function. This study aimed to investigate the relationship between renal impairment and the incidence of chemotherapy-induced neutropenia during FTD/TPI + Bmab therapy using real-world data. We retrospectively reviewed the medical records of 69 patients with metastatic colorectal cancer (mCRC) who were treated with FTD/TPI + Bmab for more than 28 days. Patients with renal impairment with an eGFR of 30-44 mL/min/1.73 m were defined as the G3b group. Seven patients (10.1%) were classified into the G3b group. Patients in the G3b group had an approximately 24% higher incidence of grade ≥ 3 neutropenia in comparison to others (71.4% vs. 46.8%), and the incidence of grade 4 neutropenia in the G3b group was significantly higher than that in others (42.9% vs. 9.7%, p = 0.042). The G3b group frequently developed grade ≥ 3 neutropenia within 30 days of the initiation of FTD/TPI + Bmab therapy. However, the duration required for neutrophil count to recover to ≥ 1500/mm and the treatment effects of the G3b group were comparable to those observed in other patients. Clinicians should pay extra attention to patients with a decreased renal function who are treated with FTD/TPI + Bmab therapy, but no special measures are required for patients with an eGFR ≥ 30 mL/min/1.73 m as no marked differences were observed in neutrophil count recovery.

摘要

尽管III期SUNLIGHT试验已证明在三氟尿苷/胸苷磷酸化酶抑制剂(FTD/TPI)基础上加用贝伐单抗(Bmab)可带来生存获益,但FDT/TPI + Bmab治疗期间频繁发生的中性粒细胞减少是临床医生关注的问题。由于TPI经肾脏排泄,肾功能受损患者发生不良事件的风险可能较高。本研究旨在利用真实世界数据调查FTD/TPI + Bmab治疗期间肾功能损害与化疗诱导的中性粒细胞减少发生率之间的关系。我们回顾性分析了69例接受FTD/TPI + Bmab治疗超过28天的转移性结直肠癌(mCRC)患者的病历。估算肾小球滤过率(eGFR)为30 - 44 mL/min/1.73 m²的肾功能损害患者被定义为G3b组。7例患者(10.1%)被归入G3b组。与其他患者相比,G3b组≥3级中性粒细胞减少的发生率高出约24%(71.4%对46.8%),且G3b组4级中性粒细胞减少的发生率显著高于其他患者(42.9%对9.7%,p = 0.042)。G3b组在FTD/TPI + Bmab治疗开始后30天内频繁发生≥3级中性粒细胞减少。然而,中性粒细胞计数恢复至≥1500/mm³所需的时间以及G3b组的治疗效果与其他患者相当。临床医生应对接受FTD/TPI + Bmab治疗的肾功能下降患者格外关注,但对于eGFR≥30 mL/min/1.73 m²的患者无需采取特殊措施,因为在中性粒细胞计数恢复方面未观察到明显差异。

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