Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital, Beijing 100191, China.
Department of General Surgery, Peking University Third Hospital, Beijing 100191, China.
Zhongguo Fei Ai Za Zhi. 2022 Mar 20;25(3):137-146. doi: 10.3779/j.issn.1009-3419.2022.101.07.
The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear.
A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A16 and UGT1A128 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A16 and UGT1A128 were detected by digital fluorescence molecular hybridization.
There were 43 patients with UGT1A16 heterozygous mutation, 26 patients with UGT1A128 heterozygous mutation, 8 patients with UGT1A16 and UGT1A128 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A16 and UGT1A128. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A128, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A16. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not.
In clinical use, heterozygous mutations of UGT1A16 and UGT1A128 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
文献建议对 UGT1A1 纯合突变患者应用 CPT-11 减剂量治疗，但 UGT1A1 杂合突变对 CPT-11 不良反应的影响尚不完全清楚。
回顾性纳入 2018 年 1 月至 2021 年 9 月于北京大学第三医院接受 CPT-11 治疗的 UGT1A1 杂合突变或野生型患者 107 例。分析 UGT1A16 和 UGT1A128 突变患者的不良反应谱。采用美国国立癌症研究所不良事件通用术语标准（NCI-CTCAE）5.0 评估不良反应。根据实体瘤反应评价标准（RECIST）1.1 评估疗效。采用数字荧光分子杂交法检测 UGT1A16 和 UGT1A128 的基因型。
43 例 UGT1A16 杂合突变，26 例 UGT1A128 杂合突变，8 例 UGT1A16 和 UGT1A128 双重杂合突变，61 例 UGT1A16 和 UGT1A128 任一基因座杂合突变。Logistic 回归分析显示，呕吐（P=0.013）和黏膜炎（P=0.005）的发生与 UGT1A128 杂合突变显著相关，呕吐严重程度（P<0.001）和中性粒细胞减少症（P=0.021）与 UGT1A16 杂合突变显著相关。在结直肠癌中，UGT1A1*6 与腹泻显著相关（P=0.005），其他不良反应谱与全患者队列相似，不同基因型患者和接受 CPT-11 减剂量治疗或未接受 CPT-11 减剂量治疗的患者的疗效和预后相似。
在临床应用中，UGT1A16 和 UGT1A128 杂合突变与 Pan-肿瘤和结直肠癌患者接受 CPT-11 治疗后的呕吐、腹泻、中性粒细胞减少和黏膜炎风险和严重程度相关。在结直肠癌中，UGT1A1*6 与 CPT-11 治疗后的腹泻显著相关，疗效和预后不受各种基因型或 CPT-11 减剂量的影响。
