UGT1A1与IP方案一线治疗广泛期SCLC疗效及不良反应研究

CLINICAL STUDY OF THE CORRELATION BETWEEN UGT1A1POLYMORPHISM AND THE SAFETY AND EFFICACY OF IRINOTECAN IN SMALL CELL LUNG CANCER PATIENTS

目的了解广泛期小细胞肺癌患者血中尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）启动子的多态性分布，并研究其多态性和伊立替康化疗不良反应、疗效之间的关系。方法收集采用伊立替康加顺铂化疗患者全血标本，直接测序分析UGT1A1＊X-28TATA盒基因序列；并与化疗不良反应、疗效进行分析。结果36例患者进行UGT1A1＊28TATA基因启动子检测，UGTIA1＊28野生纯合型（TA6／6）27例，占75％；突变杂合型（TA6／7）7例，占19．4％；突变纯合型（TA7／7）2例，占5．6％。UGT1A1基因突变纯合型（TA7／7））患者发生Ⅲ度迟发型腹泻1倒，2例皆发生Ⅲ度粒细胞减少。UGT1A1基因突变杂合型（TA6／7）发生Ⅲ度迟发型腹泻1例，Ⅲ度粒细胞减少1例。UGTIA1基因野生纯合型（TA6／6）无Ⅲ度迟发型腹泻和Ⅲ度中性粒细胞减少发生，Ⅰ～Ⅱ度迟发型腹泻3例，I～Ⅱ度粒细胞减少5例。全部患者未发生Ⅲ度以上恶心、呕吐、食欲不振、乏力、腹泻等不良反应。UGT1A1基因突变纯合型（TA7／7）CR0例，PR1例；UGT1A1基因突变杂舍型（TA6／7）CR1例，PR3例；UGT1A1基因野生纯合型（TA6／6）CR3例，PR15例。结论UGT1A1＊28突变纯合型（TA7／7）可能增加伊立替康所致3度及以上延迟性腹泻和中性粒细胞减少。

Objective To investigate the polymorphism of uridine diphosphate glucuronosyltrasferase （UGT） 1A1 gene and its possibility as the predictor of safety and efficacy of IP regimen as first- line treat- ment in extensive- stage small cell lung cancer patients. Methods Peripheral blood specimens for genomic DNA analysis from the ED- SCLC patients were collected before IP chemotherapy and the UGTIA1 genotypes were determined by direct sequencing analysis using genomic DNA extraction. The adverse events were recorded to compare the incidence of grades 3 and 4 adverse events. Results Totally 27（75%） were i- dentified as having homozygous wildtype TA6/6 in the promoter region at position 28 of the UGT1A1 gene,7（19.4% ） were found to have heterozygous type TA6/7, and 2（5.6% ） carried homozygous mutanttype TAT/7. There were 1 case and 2 cases with grade 3 diarrhea and neutropenia in patients with homozygous mutant- type TAT/7 ; There were 1 case and 1 case with grade 3 diarrhea and neutropenia respectively in patients with heterozygous mutanttype TA6/7; There were 0 case with grade 3 diarrhea and neutropenia respectively in patients with wild- type TA6/6. There were 0, i and 1, 3 and 3, 15 cases with CR,PR respectively in patients with homozygous mutanttype TAT/7 and heterozygous mutant - type TA6/7 and homozygous wild - type TA6/6. Conclusion Irinoteean plus platinum as first - line chemotherapy treatment is effective and tolerable for ED- SCLC. Detecting UGT1 A1 ＊ 28 gene polymorphism can guide individualized treatment of patients with extensivestage small cell lung cancer.