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目的观察FOLFIRI方案治疗转移性结直肠癌的疗效、副反应及UGT1A1基因多态性与与副反应的相关性。方法对96例确诊的晚期结直肠癌患者,采用FOLFIRI方案治疗,观察近期疗效和副反应及UGT1A1基因多态性与副反应相关性。结果 96例患者用药后获得PR58例,SD 24例,PD 14例,无1例获得CR。ORR60.4%,DCR85.4%,所有患者均获随访,中位TTP 6.1月。主要毒副反应为骨髓抑制,其中中性粒细胞减少发生率为88.5%;脱发发生率较高,总发生率为83.3%;迟发性腹泻发生率为19.8%,均得到了有效的控制。检测UGT1A1基因多态性12例患者中,(TA)6/(TA)6UGT1A1*1/*1纯合野生基因型9例,发生腹泻为1例,为Ⅰ度。(TA)6/(TA)7UGT1A1*28/*1杂合基因型3例,发生腹泻2例,其中1例为Ⅲ度腹泻。结论 FOLFlRI方案是治疗常规化疗失败晚期结直肠癌的有效化疗方案,缓解率较高,迟发性腹泻和中性粒细胞减少为其主要不良反应。UGT1A1启动子区TATA盒基因多态性(TA)6/(TA)7杂合状态可以增加患者发生严重腹泻的风险。
Objective To observe the curative effect, side effects, UGT1A1 gene polymorphism and side effects of FOLFIRI regimen in the treatment of metastatic colorectal cancer. Methods Ninety-six patients with advanced colorectal cancer who were diagnosed were treated with FOLFIRI regimen. The curative effect and side effects and the association of UGT1A1 gene polymorphism with side effects were observed. Results 96 patients received PR58 cases, SD 24 cases, PD 14 cases, no case of CR was obtained. ORR60.4%, DCR85.4%, all patients were followed up, median TTP 6.1 months. The main toxicities were myelosuppression. The incidence of neutropenia was 88.5%. The incidence of alopecia was high, the total incidence was 83.3%. The incidence of delayed diarrhea was 19.8%, which were effectively controlled. Among the 12 patients with UGT1A1 gene polymorphism, 9 (TA) 6 / (TA) 6UGT1A1 * 1 / * 1 homozygous wild type genotypes were detected in 9 cases. (TA) 6 / (TA) 7UGT1A1 * 28 / * 1 heterozygous genotype in 3 cases, diarrhea in 2 cases, of which 1 case of Ⅲ degree diarrhea. Conclusion The FOLFlRI regimen is an effective chemotherapy regimen for the treatment of advanced colorectal cancer with conventional chemotherapy failure. The high remission rate, delayed diarrhea and neutropenia are the main adverse reactions. The heterozygosity of the TATA box gene polymorphism (TA) 6 / (TA) 7 in the UGT1A1 promoter increases the risk of severe diarrhea in patients.