<br>局部晚期直肠癌新辅助放化疗期间 UGT1A1 基因型指导的伊立替康给药：SN-38 浓度的前瞻性分析,International Journal of Cancer

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局部晚期直肠癌新辅助放化疗期间 UGT1A1 基因型指导的伊立替康给药：SN-38 浓度的前瞻性分析
International Journal of Cancer ( IF 5.7 ) Pub Date : 2023-12-29 , DOI: 10.1002/ijc.34826
Pei-Cheng Jiang _{1,

2} , Shuo-Wen Wang ₃ , Chao Li ₄ , Jin Fan ₄ , Ji Zhu _{1,

2,

5}

Affiliation

伊立替康在直肠癌新辅助放化疗（nCRT）中发挥着至关重要的作用，但其最佳剂量仍不清楚。在这项研究中，我们纳入了 101 名符合条件的患者，其 UGT1A1*28 基因型为 UGT1A1*1*1 (74.3%) 和 UGT1A1*1*28 (25.7%)，UGT1A1*6 基因型为 GG (63.4%)、GA (32.7%)。 %) 和 AA (3.9%)。所有患者均接受术前放疗（50 Gy/25 次），同时接受伊立替康（UGT1A1*1*1：80 mg/m ² ；UGT1A1*1*28：65 mg/m ² ）和卡培他滨（CapIri）。在给药后 1.5、24 和 49 小时测量 SN-38 浓度。根据 SN-38 浓度将患者分为四组（Q1-Q4）。完全缓解（CR）率是主要终点。分析表明，49 小时 SN-38 浓度对于预测疗效和毒性来说是相对最佳的。 Q4 组的 CR 率显着高于 Q1 组 ( p = .019)，但不良事件发生率也更高 ( p = .009)。我们筛选了推荐的 49 小时 SN-38，浓度范围为 0.5–1.0 ng/mL。我们还验证了 UGT1A1*6 多态性与 SN-38 浓度之间的相关性以及伊立替康的临床疗效。总之，我们的研究确定了监测 SN38 浓度的相对最佳时间点和浓度范围，并揭示了 UGT1A1*6 和 UGT1A1*28 多态性在指导伊立替康给药中的临床意义，为个性化伊立替康给药提供了有意义的见解。

"点击查看英文标题和摘要"

UGT1A1 genotype-guided irinotecan dosing during neoadjuvant chemoradiotherapy for locally advanced rectal cancer: A prospective analysis of SN-38 concentration

Irinotecan plays a crucial role in the neoadjuvant chemoradiotherapy (nCRT) of rectal cancer, but its optimal dosing is still unclear. In this study, we included 101 eligible patients with the UGT1A1*28 genotype of UGT1A1*1*1 (74.3%) and UGT1A1*1*28 (25.7%) and UGT1A1*6 genotypes of GG (63.4%), GA (32.7%), and AA (3.9%). All patients received preoperative radiotherapy (50 Gy/25 fractions) with concurrent irinotecan (UGT1A1*1*1: 80 mg/m²; UGT1A1*1*28: 65 mg/m²) and capecitabine (CapIri). SN-38 concentrations were measured at 1.5, 24, and 49 h post-administration. Patients were divided into four groups (Q1–Q4) based on the SN-38 concentration. The complete-response (CR) rate was the primary endpoint. The analysis demonstrated that the 49 h SN-38 concentration was relatively optimal for predicting efficacy and toxicity. The Q4 group had a significantly higher CR rate than the Q1 group (p = .019), but also higher rates of adverse events (p = .009). We screened the recommended 49 h SN-38, with a 0.5–1.0 ng/mL concentration range. We also validated the correlation between UGT1A1*6 polymorphism and SN-38 concentration, along with the clinical efficacy of irinotecan. In conclusion, our study identified the relatively optimal timepoint and concentration range for monitoring SN38 concentrations and revealed the clinical significance of UGT1A1*6 and UGT1A1*28 polymorphisms in guiding irinotecan administration, offering meaningful insights for personalised irinotecan dosing.

更新日期：2023-12-29

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