近年来，DPYD 指导剂量提高了基于氟嘧啶的化疗的安全性。然而，在接受卡培他滨治疗的不携带 DPYD 变异等位基因的患者中，约 23% 仍存在严重毒性。因此，我们根据患者相关和治疗相关因素开发了一个预测模型，旨在估计发生严重卡培他滨相关毒性的风险。该列线图是使用两项大型临床试验（NCT00838370 和 NCT02324452）的数据开发的。携带 DPYD 变异等位基因（DPYD*2A、c.1236G>a、c.2846A>T 和 c.1679T>G）的癌症患者被排除在外。使用基于先前发现的预定预测因子（包括年龄、性别、体表面积、治疗方案类型和肌酐水平）的单变量和多变量逻辑回归来绘制列线图。使用引导重采样和交叉验证对开发的模型进行内部验证。该模型未经外部或临床验证。总共纳入了 2147 名接受基于卡培他滨化疗方案治疗的 DPYD 野生型癌症患者，其中 1745 名患者的完整数据可用并用于绘制列线图。单变量和多变量逻辑回归显示，年龄、性别和治疗方案类型是 DPYD 野生型患者严重卡培他滨相关毒性的强有力预测因素。内部验证显示一致性指数为 0.68，这表明预测严重卡培他滨相关毒性具有良好的辨别能力。开发的列线图包括现成的参数，可能是临床医生评估在接受基于卡培他滨的抗癌方案治疗的无已知风险 DPYD 变异等位基因的患者中发生严重卡培他滨相关毒性的风险的有用工具。本文受版权保护。版权所有。

DPYD-guided dosing has improved the safety of fluoropyrimidine-based chemotherapy in recent years. However, severe toxicity remains in ~23% of patients not carrying DPYD variant alleles treated with capecitabine. Therefore, we developed a predictive model based on patient-related and treatment-related factors aimed at estimating the risk of developing severe capecitabine-related toxicity. The nomogram was developed using data from two large clinical trials (NCT00838370 and NCT02324452). Cancer patients carrying a DPYD variant allele (DPYD*2A, c.1236G>a, c.2846A>T, and c.1679T>G) were excluded. Univariable and multivariable logistic regression using predetermined predictors based on previous findings including age, sex, body surface area, type of treatment regimen, and creatinine levels were used to develop the nomogram. The developed model was internally validated using bootstrap resampling and cross-validation. This model was not externally or clinically validated. A total of 2147 DPYD wild-type patients with cancer treated with capecitabine-based chemotherapy regimens were included of which complete data of 1745 patients was available and used for the development of the nomogram. Univariable and multivariable logistic regression showed that age, sex, and type of treatment regimen were strong predictors of severe capecitabine-related toxicity in DPYD wild-type patients. Internal validation demonstrated a concordance index of 0.68 which indicates a good discriminative ability for prediction of severe capecitabine-related toxicity. The developed nomogram includes readily available parameters and may be a helpful tool for clinicians to assess the risk of developing severe capecitabine-related toxicity in patients without known risk DPYD variant alleles treated with capecitabine-based anticancer regimens.This article is protected by copyright. All rights reserved.