Dias M M, Pignon J-P, Karapetis C S, Boige V, Glimelius B, Kweekel D M, Lara P N, Laurent-Puig P, Martinez-Balibrea E, Páez D, Punt C J A, Redman M W, Toffoli G, Wadelius M, McKinnon R A, Sorich M J
School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
Meta-analysis Unit, Department of Biostatistics and Epidemiology, Gustave-Roussy, Villejuif, France.
Pharmacogenomics J. 2014 Oct;14(5):424-31. doi: 10.1038/tpj.2014.16. Epub 2014 Apr 8.
To date, studies of irinotecan pharmacogenetics have mostly focused on the effect of the UGT1A128 allele on irinotecan-related toxicity. However, the clinical utility of routine UGT1A128 genotyping to pre-emptively adjust irinotecan dosage is dependent upon whether UGT1A128 also affects patient survival following irinotecan therapy. Previous observational studies evaluating the influence of UGT1A128 on survival have shown contradictory results. A systematic review and meta-analysis of both published and unpublished data were performed to summarize the available evidence of the relationship between the UGT1A128 allele and patient survival related to irinotecan therapy. Overall and progression-free survival meta-analysis data were available for 1524 patients and 1494 patients, respectively. The difference in the survival between patients of different UGT1A128 genotypes (homozygous, heterozygous or wild-type) who had received irinotecan was not found to be statistically significant. There was also no evidence of irinotecan dose, regimen or line of therapy having an impact on this association.
迄今为止，伊立替康药物遗传学研究主要聚焦于UGT1A128等位基因对伊立替康相关毒性的影响。然而，常规UGT1A128基因分型用于预先调整伊立替康剂量的临床实用性取决于UGT1A128是否也会影响伊立替康治疗后的患者生存率。此前评估UGT1A128对生存率影响的观察性研究结果相互矛盾。我们对已发表和未发表的数据进行了系统评价和荟萃分析，以总结UGT1A128等位基因与伊立替康治疗相关患者生存率之间关系的现有证据。分别有1524例患者和1494例患者的总生存和无进展生存荟萃分析数据。未发现接受伊立替康治疗的不同UGT1A128基因型（纯合子、杂合子或野生型）患者之间的生存差异具有统计学意义。也没有证据表明伊立替康剂量、治疗方案或治疗线数对这种关联有影响。
