Clinical Observations on Associations Between the UGT1A1 Genotype and Severe Toxicity of Irinotecan

Lu, Yan-Yan; Huang, Xin-En; Wu, Xue-Yan; Cao, Jie; Liu, Jin; Wang, Lin; Xiang, Jin

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자료유형: 학술저널

저자정보: Lu, Yan-Yan (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jingsu Institute of Cancer Research) Huang, Xin-En (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jingsu Institute of Cancer Research) Wu, Xue-Yan (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jingsu Institute of Cancer Research) Cao, Jie (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jingsu Institute of Cancer Research) Liu, Jin (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jingsu Institute of Cancer Research) Wang, Lin (Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jingsu Institute of Cancer Research) Xiang, Jin (Department of Research, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University & Jingsu Institute of Cancer Research)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제15권 제7호

발행연도: 2014.1

수록면: 3,335 - 3,341 (7page)

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Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia was 13.4%and also highest in patients with the TA 6/7 genotype (4 of 22 patients; 18.2%) but without significance (p>0.05). The retreatment total bilirubin levels were significantly higher in TA6/7 patients (mean, $12.75{\mu}mol/L$) with compared to TA6/6 (mean, $9.92{\mu}mol/L$) with p<0.05. Conclusions: Our study support the conclusion that patients with a $UGT1A1^*28$ allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the $UGT1A1^*28$ allele (s) did not increase severe neutropenia. Higher serum total bilirubin is an indication that patients UGT1A1 genotype is not wild-type, with significance for clinic usage of CPT-11.

#CPT-11 #UGT1A1 genotype #toxicity

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Lu, Yan-Yan

소속기관 Department of Chemotherapy, the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University &am