Department of Haematology & Oncology, Ludwig-Maximilians University of Munich, Campus Grosshadern, Marchioninistr 15, Munich 81377, Germany.
World J Gastroenterol. 2009 Oct 28;15(40):5058-66. doi: 10.3748/wjg.15.5058.
To investigate the correlation between uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphisms and irinotecan-associated side effects and parameters of drug efficacy in patients with metastatic colorectal cancer (mCRC) receiving a low-dose weekly irinotecan chemotherapeutic regimen.
Genotypes were retrospectively evaluated by gene scan analysis on the ABI 310 sequencer of the TATAA box in the promoter region of the UGT1A1 gene in blood samples from 105 patients who had received 1st line irinotecan-based chemotherapy for mCRC.
The distribution of the genotypes was as follows: wild type genotype (WT) (6/6) 39.0%, heterozygous genotype (6/7) 49.5%, and homozygous genotype (7/7) 9.5%. The overall response rate (OR) was similar between patients carrying the (6/7, 7/7) or the WT genotype (6/6) (44.3% vs 43.2%, P = 0.75). Neither time to progression [(TTP) 8.1 vs 8.2 mo, P = 0.97] nor overall survival [(OS) 21.2 vs 18.9 mo, P = 0.73] differed significantly in patients who carried the (6/6) when compared to the (6/7, 7/7) genotype. No significant differences in toxicity were observed: Grade 3 and 4 delayed diarrhoea [(6/7, 7/7) vs (6/6); 13.0% vs 6.2%, P =0.08], treatment delays [(6/7, 7/7) vs (6/6); 25.1% vs 19.3%, P =0.24] or dose reductions [(6/7, 7/7) vs (6/6); 21.5% vs 27.2%, P =0.07].
This analysis demonstrates the non-significant influence of the UGT1A1 gene polymorphism on efficacy and rate of irinotecan-associated toxicity in mCRC patients receiving low-dose irinotecan based chemotherapy.
研究尿苷二磷酸葡萄糖醛酸基转移酶 1A1（UGT1A1）基因多态性与转移性结直肠癌（mCRC）患者接受低剂量每周伊立替康化疗方案相关的伊立替康相关副作用和药物疗效参数之间的相关性。
通过基因扫描分析，对 105 例接受一线伊立替康为基础化疗的 mCRC 患者血液样本中的 TATAA 框在 UGT1A1 基因启动子区域的 ABI 310 测序仪上对基因型进行回顾性评估。
基因型分布如下：野生型基因型（WT）（6/6）39.0%，杂合基因型（6/7）49.5%，纯合基因型（7/7）9.5%。携带（6/7、7/7）或 WT 基因型（6/6）的患者总体缓解率（OR）相似（44.3% vs 43.2%，P = 0.75）。携带（6/6）与（6/7、7/7）基因型的患者之间无进展时间（TTP）[8.1 vs 8.2 mo，P = 0.97]和总生存（OS）[21.2 vs 18.9 mo，P = 0.73]差异有统计学意义。未观察到毒性差异：3 级和 4 级迟发性腹泻[（6/7、7/7）vs（6/6）；13.0% vs 6.2%，P = 0.08]、治疗延迟[（6/7、7/7）vs（6/6）；25.1% vs 19.3%，P = 0.24]或剂量减少[（6/7、7/7）vs（6/6）；21.5% vs 27.2%，P = 0.07]。
该分析表明 UGT1A1 基因多态性对接受低剂量伊立替康为基础化疗的 mCRC 患者的疗效和伊立替康相关毒性发生率无显著影响。
