DPYD 导向的氟嘧啶类药物剂量个体化可提高 DPYD 变异等位基因携带者的患者安全性。然而，这些患者的治疗结果影响尚不明确。因此，本研究采用回顾性对比配对生存分析，比较了接受减量剂量的 DPYD 变异携带者和接受标准剂量氟嘧啶类药物的 DPYD 野生型对照组之间的无进展生存期（PFS）和总生存期（OS）。从一项前瞻性多中心研究（ClinicalTrials.gov 登记号: NCT02324452）中获取了 DPYD 变异携带者接受 25% (c.1236G>A 和 c.2846A>T) 或 50% (DPYD*2A 和 c.1679T>G) 减量剂量的数据，以及在临床例行护理中发现的接受相似减量剂量氟嘧啶类药物治疗的 DPYD 变异携带者的数据。每个 DPYD 变异携带者被匹配三个接受标准剂量氟嘧啶类药物治疗的 DPYD 野生型对照组。采用 Kaplan-Meier 估计和 Cox 回归进行生存分析。总共有 156 名 DPYD 变异携带者和 775 名 DPYD 野生型对照组可供分析。61 名 c.1236G>A 携带者、25 名 DPYD*2A 携带者、13 名 c.2846A>T 携带者和合并分析中的 93 名 DPYD 变异携带者分别能够与三个独特的 DPYD 野生型对照组进行匹配。对于合并分析的 DPYD 变异携带者，DPYD 导向的剂量个体化不会对 PFS（风险比 [HR], 1.23; 95% CI, 1.00 to 1.51; P = .053）和 OS（风险比 [HR], 0.95; 95% CI, 0.75 to 1.51; P = .698）产生不良影响。在亚组分析中，c.1236G>A 变异携带者的 PFS 显著较短（HR, 1.43; 95% CI, 1.10 to 1.86; P = .007），而 DPYD*2A 和 c.2846A>T 携带者无差异。在这一探索性分析中，DPYD 导向的氟嘧啶类药物剂量个体化不会对合并分析的 DPYD 变异携带者的 PFS 和 OS 产生不良影响。建议对 c.1236G>A 携带者在接受减量起始剂量时进行密切监测，并根据毒性进行早期剂量调整。

DPYD-guided fluoropyrimidine dosing improves patient safety in carriers of DPYD variant alleles. However, the impact on treatment outcome in these patients is largely unknown. Therefore, progression-free survival (PFS) and overall survival (OS) were compared between DPYD variant carriers treated with a reduced dose and DPYD wild-type controls receiving a full fluoropyrimidine dose in a retrospective matched-pair survival analysis.Data from a prospective multicenter study (ClinicalTrials.gov identifier: NCT02324452) in which DPYD variant carriers received a 25% (c.1236G>A and c.2846A>T) or 50% (DPYD*2A and c.1679T>G) reduced dose and data from DPYD variant carriers treated with a similarly reduced dose of fluoropyrimidines identified during routine clinical care were obtained. Each DPYD variant carrier was matched to three DPYD wild-type controls treated with a standard dose. Survival analyses were performed using Kaplan-Meier estimates and Cox regression.In total, 156 DPYD variant carriers and 775 DPYD wild-type controls were available for analysis. Sixty-one c.1236G>A, 25 DPYD*2A, 13 c.2846A>T, and-when pooled-93 DPYD variant carriers could each be matched to three unique DPYD wild-type controls. For pooled DPYD variant carriers, PFS (hazard ratio [HR], 1.23; 95% CI, 1.00 to 1.51; P = .053) and OS (HR, 0.95; 95% CI, 0.75 to 1.51; P = .698) were not negatively affected by DPYD-guided dose individualization. In the subgroup analyses, a shorter PFS (HR, 1.43; 95% CI, 1.10 to 1.86; P = .007) was found in c.1236G>A variant carriers, whereas no differences were found for DPYD*2A and c.2846A>T carriers.In this exploratory analysis, DPYD-guided fluoropyrimidine dosing does not negatively affect PFS and OS in pooled DPYD variant carriers. Close monitoring with early dose modifications based on toxicity is recommended, especially for c.1236G>A carriers receiving a reduced starting dose.