相对剂量强度对S-1所致骨髓抑制的影响：回顾性观察研究

Impact of relative dose intensity on bone marrow suppression induced by S-1: retrospective observational study.

作者信息

Hirai Toshinori, Ogawa Ryuichi, Yamaga Ryosuke, Itoh Toshimasa

机构信息

1Department of Pharmacy, Tokyo Women's Medical University Medical Center East, 2-1-10, Nishiogu, Arakawa-ku, Tokyo, 116-0011 Japan.

2Department of Pharmacotherapy, Meiji Pharmaceutical University, Tokyo, Japan.

出版信息

J Pharm Health Care Sci. 2018 Dec 3;4:30. doi: 10.1186/s40780-018-0127-x. eCollection 2018.

DOI:10.1186/s40780-018-0127-x

PMID:30524750

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6276246/

Abstract

BACKGROUND

S-1 (a combination of tegafur, gimeracil, and oteracil) is used to treat various cancers. Bone marrow suppression is a dose-limiting toxicity of S-1. The relationship between relative dose intensity (RDI) and bone marrow suppression has not been investigated. Hence, we aimed to elucidate the threshold for RDI to identify bone marrow suppression induced by S-1.

METHODS

In this retrospective cohort study, patients who initiated S-1 treatment at Tokyo Women's Medical University, Medical Center East between June 2015 and June 2017 were included. Bone marrow suppression induced by S-1 was assessed using Common Terminology Criteria for Adverse Events version 4.0. The relationships between grade 3 or higher bone marrow suppression induced by S-1 and RDIs (i.e., 70, 75, and 80%) were investigated using the multivariate Cox proportional hazard model.

RESULTS

We identified 143 patients in this study. The median RDI was 78.8%. Bone marrow suppression induced by S-1 developed in 19 (13.3%) patients. The multivariate Cox proportional hazard model revealed that grade ≥ 2 lymphocytopenia was associated with bone marrow suppression induced by S-1 regardless of the threshold for RDI. In addition, RDI > 75% [hazard ratio (HR) = 1.71, < 0.05] and RDI > 80% (HR = 1.65, < 0.05) were associated with bone marrow suppression induced by S-1.

CONCLUSIONS

Reduced dose of S-1 still has the risk of developing bone marrow suppression. Clinicians should assess RDI to identify high risk patients with bone marrow suppression induced by S-1.

摘要

背景

S-1（替加氟、吉美嘧啶和奥替拉西的组合）用于治疗多种癌症。骨髓抑制是S-1的剂量限制性毒性。相对剂量强度（RDI）与骨髓抑制之间的关系尚未得到研究。因此，我们旨在阐明RDI的阈值，以识别S-1诱导的骨髓抑制。

方法

在这项回顾性队列研究中，纳入了2015年6月至2017年6月在东京女子医科大学东医疗中心开始接受S-1治疗的患者。使用不良事件通用术语标准第4.0版评估S-1诱导的骨髓抑制。使用多变量Cox比例风险模型研究S-1诱导的3级或更高等级骨髓抑制与RDI（即70%、75%和80%）之间的关系。

结果

我们在本研究中确定了143例患者。RDI的中位数为78.8%。19例（13.3%）患者发生了S-1诱导的骨髓抑制。多变量Cox比例风险模型显示，无论RDI阈值如何，≥2级淋巴细胞减少与S-1诱导的骨髓抑制相关。此外，RDI>75%[风险比（HR）=1.71，P<0.05]和RDI>80%（HR=1.65，P<0.05）与S-1诱导的骨髓抑制相关。