Affiliated Hospital Cancer Center, Academy of Military Medical Science, Beijing 100071, China.
World J Gastroenterol. 2013 Jun 28;19(24):3899-903. doi: 10.3748/wjg.v19.i24.3899.
Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bearing UGT1A1 28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of irinotecan are advised that patients with UGT1A1 28 (TA 7/7) should start with a reduced dose of irinotecan, although a particular dose is not specified. Research in Asian countries has shown a lower incidence of UGT1A1 28 (TA 7/7), while UGT1A1 6 (A/A) is more often found and is associated with severe irinotecan-related neutropenia. We report here a case of a metastatic colorectal cancer patient who is heterozygous for the UGT1A1 28 polymorphism (TA 6/7) as well as the UGT1A1 6 polymorphism (G/A). The patient was treated with FOLFIRI for 9 cycles and underwent two irinotecan dose reductions according to pharmacokinetic data regarding exposure to the active metabolite, SN-38. Simultaneous heterozygous UGT1A1 28 and UGT1A1 6 polymorphisms may produce higher exposure to SN-38 and a higher risk of adverse effects related to irinotecan. Additional studies will be necessary to determine the optimal starting dose of irinotecan for patients with both UGT1A1 28 and UGT1A1 6 polymorphisms.
许多研究已经证实了 UGT1A1 对伊立替康毒性的影响。特别是，携带 UGT1A1 28（TA7/7）的患者发生严重中性粒细胞减少和腹泻的风险更高。基于此，伊立替康的处方医生建议，UGT1A1 28（TA7/7）的患者应起始使用较低剂量的伊立替康，尽管未指定特定剂量。亚洲国家的研究表明 UGT1A1 28（TA7/7）的发生率较低，而 UGT1A1 6（A/A）更为常见，与严重的伊立替康相关中性粒细胞减少有关。我们在此报告一例转移性结直肠癌患者，其 UGT1A1 28 多态性（TA6/7）和 UGT1A1 6 多态性（G/A）均为杂合子。该患者接受了 9 个周期的 FOLFIRI 治疗，并根据活性代谢物 SN-38 暴露的药代动力学数据进行了两次伊立替康剂量减少。UGT1A1 28 和 UGT1A1 6 同时存在杂合子多态性可能会导致 SN-38 暴露增加，从而增加与伊立替康相关的不良反应风险。需要进一步的研究来确定同时携带 UGT1A1 28 和 UGT1A1 6 多态性的患者使用伊立替康的最佳起始剂量。
