晚期胃癌患者ERCC1 TUBB3 TYMS三基因联合检测指导的DCF方案个体化化疗的研究

Individualized Chemotherapeutic Regimen with Docetaxel,Cisplatin,and 5-FU Guided by Combined Detection of ERCC1,TUBB3,and TYMS Genes in Patients with Advanced Gastric Cancer

目的:根据ERCC1、TUBB3、TYMS基因mRNA表达水平选择Docetaxel、DDP、5-FU组成相应的化疗方案对晚期胃癌进行化疗的疗效、不良反应及生存期评价。方法:前瞻性纳入于本院2009年5月至2012年5月初治的晚期胃癌的患者120例,随机分为二组:研究组(60例):采用分支DNA-液相芯片技术定量检测胃癌组织ERCC1、TUBB3、TYMS基因mRNA表达水平,并根据检测结果,选择药物Docetaxel、DDP、5-FU组成相应敏感的化疗方案对其进行化疗;对照组(60例):予以DCF方案化疗,观察两组疗效、不良反应,中位疾病进展时间(mTTP)及中位生存时间(mOS)。结果:研究组、对照组化疗有效率分别为55%、50%,差异无统计学意义(P=0.357)。两组mTTP分别为10个月和7个月,差异无统计学意义(P=0.091)。两组mOS为13.7个月和11.6个月,差异有统计学意义(P=0.004)。两组间不良反应相似,但对照组不良反应Ⅲ°～Ⅳ°明显高于研究组,差异有统计学意义(P<0.05)。结论:晚期胃癌根据ERCC1、TUBB3、TYMS基因mRNA表达水平检测结果选择药物Docetaxel、DDP、5-FU组成相应敏感的化疗方案进行化疗,疗效非劣性、不良反应降低,且改善mOS。

Objective： This work aimed to comparatively analyze efficacy, toxicity, and survival in patients with advanced gas-tric cancer treated with the chemotherapeutic agents docetaxel （D）, cisplatin （C）, and 5-FU （F） using the mRNA expression levels of the ERCC 1, TUBB3, and TYMS genes. Methods：Clinical data of120 patients who were admitted to our hospital between May2009and May 2012were analyzed. These patients were randomly divided into two treatment groups, namely, the tumor group （TG） （n=60） and the control group （CG） （ n=60）. Branched-DNA liquid chip quantitative analysis was used in the TG to detect the mRNA expression lev -els of ERCC1, TUBB3, and TYMS, and the relatively sensitive D, C, and F were respectively chosen according to treatment outcomes. DCF therapy was used to treat the CG. Treatment efficiency, toxicity, median time to progression （TTP）, and median overall survival （mOS） time were observed and analyzed. Results：The rates of chemotherapeutic efficiency were 55% and 50% in the TG and CG, re-spectively, and the difference was not statistically significant （ P=0.357）. TTP did not statistically differ between the groups （TG, 10 months; GC,7 months） （ P=0.091）. The mOS rates in the TG and CG were 13.7 and 11 .6 months, and the difference was significant （P= 0.004）. Adverse effects were similar in the groups, but the lesions in the TG were limited to Grades Ⅰand Ⅱ, whereas those in the CG reached Grades Ⅲand Ⅳ. The adverse reactions were significantly higher in the CG than in the TG, with the difference being statisti -cally significant （P〈0.05）. Conclusions： The chemotherapeutic DCF regimen is efficient and has reduced toxicity for patients with ad -vanced gastric cancer according to the mRNA expression levels of ERCC1, TUBB3, and TYMS. It can be used to improve mOS.