Cruz Joseph E, Saksena Rujuta, Jabbour Salma K, Nosher John L, Hermes-DeSantis Evelyn, Moss Rebecca A
Rutgers, The State University of New Jersey, Piscataway, NJ, USA
Overlook Hospital, Summit, NJ, USA.
Ann Pharmacother. 2014 Dec;48(12):1646-50. doi: 10.1177/1060028014550646. Epub 2014 Sep 8.
To report a case of systemic irinotecan toxicity following regional transarterial chemoembolization with drug-eluting beads loaded with irinotecan (DEBIRI-TACE) in a patient later found to have a homozygous mutation for UGT1A1*28.
An 80-year-old woman presented with a cecal colon cancer with synchronous metastases to the liver. After resection of the primary tumor, the patient underwent DEBIRI-TACE with 100 mg of irinotecan to treat the residual disease in the liver. A week after this procedure, the patient developed grade 4 neutropenia, and later, alopecia. Eventually, it was found that the patient had a mutation of UDP glucuronosyltransferase 1 family polypeptide A1 (UGT1A1), which provided a reasonable explanation for the observed reaction.
The toxic effects of irinotecan are well understood. Patients with genetic polymorphisms of the genes encoding for the enzyme UGT1A1 may have increased incidence of irinotecan-associated toxicities because of decreased clearance of the active metabolite SN38 via the glucuronidation pathway. To date, there have been limited publications describing systemic adverse events following TACE or DEBIRI-TACE and, based on a thorough literature search, none following these procedures in patients with UGT1A1 polymorphisms. Based on the scoring results of the Naranjo algorithm (7), we are confident in attributing the observed reaction to the patient's genetic polymorphism.
Although genetic testing prior to the initiation of irinotecan therapy is not currently recommended, assessment of UGT1A1 polymorphism is warranted when severe adverse events typical of systemic therapy manifest following DEBIRI-TACE.
报告1例在接受载有伊立替康的药物洗脱微球经动脉化疗栓塞术（DEBIRI-TACE）后出现全身伊立替康毒性反应的病例，该患者后来被发现存在UGT1A1*28纯合突变。
一名80岁女性因盲肠癌伴肝脏同步转移就诊。在切除原发肿瘤后，患者接受了100 mg伊立替康的DEBIRI-TACE治疗肝脏残留病灶。该操作一周后，患者出现4级中性粒细胞减少，随后出现脱发。最终发现患者存在尿苷二磷酸葡萄糖醛酸基转移酶1家族多肽A1（UGT1A1）突变，这为观察到的反应提供了合理的解释。
伊立替康的毒性作用已为人熟知。编码UGT1A1酶的基因存在基因多态性的患者，由于活性代谢产物SN38通过葡萄糖醛酸化途径的清除减少，伊立替康相关毒性的发生率可能会增加。迄今为止，描述TACE或DEBIRI-TACE后全身不良事件的出版物有限，并且经过全面的文献检索，在UGT1A1基因多态性患者中进行这些操作后未见相关报道。根据Naranjo算法的评分结果（7分），我们确信观察到的反应可归因于患者的基因多态性。
虽然目前不建议在开始伊立替康治疗前进行基因检测，但在DEBIRI-TACE后出现全身治疗典型的严重不良事件时，有必要评估UGT1A1基因多态性。
