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伊立替康化疗相关性腹泻发生的特点与危险因素分析
梅丹, 陆俊国, 顾海娟, 郭小红, 徐艳艳, 倪美鑫
中国医院药学杂志 ›› 2019, Vol. 39 ›› Issue (2) : 191-195.
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伊立替康化疗相关性腹泻发生的特点与危险因素分析
Analysis on characteristics and risk factors of irinotecan chemotherapy induced diarrhea
目的：探讨伊立替康化疗相关性腹泻发生的特点与危险因素，提高伊立替康临床应用安全性。方法：收集2014年1月至2016年6月以伊立替康为基础的化疗方案治疗的肿瘤患者信息，分析患者性别、年龄、烟酒史、原发灶部位、伊立替康剂量、UGT1A1基因多态性等临床特征与腹泻发生率、腹泻严重程度的关系，总结伊立替康致化疗相关性腹泻的危险因素。结果：共175例使用含伊立替康方案化疗的患者纳入分析，男性105例，女性70例，腹泻发生率为25.7%（45/175），其中早发性腹泻7例（4.0%），迟发性腹泻38例（21.7%）；轻中度腹泻（I~Ⅱ级）36例（20.6%），严重腹泻（Ⅲ~IV级）9例（5.1%）。严重腹泻均为迟发性腹泻，发生于给药后5～14 d。高龄（≥65岁）是腹泻发生的危险因素（P=0.02）；伊立替康联合铂类化疗时严重腹泻发生率为17.0%（8/47），高于FOLFIRI方案（P=0.003）；联合奥沙利铂化疗的严重腹泻率为40%（4/10），高于联合其他铂类，但无统计学差异（P=0.22）；患者性别、烟酒史、原发灶部位、伊立替康剂量、UGT1A1基因多态性对腹泻发生率和发生的严重程度无影响。结论：高龄（≥65岁）患者使用伊立替康为主的化疗方案治疗时发生腹泻的风险较高，伊立替康联合铂类化疗时需警惕严重腹泻的发生。
OBJECTIVE To explore the characteristics and relative risk factors of irinotecan-induced diarrhea, and improve the safety profiles of irinotecan in clinical use.METHODS Demographics, baseline characteristics and clinical responses of patients treated with irinotecan in our hospital were collected from January 2014 to June 2016. Subsequently, relationships between incidence or severity of diarrhea and gender, age, history of cigarette smoking and alcohol drinking, disease types, dose of irinotecan, UGT1A1 gene polymorphism were analyzed statistically by SPSS.RESULTS Totally 175 cases were collected, including 105 male and 75 female patients. Total incidence of irinotecan-induced diarrhea was 25.7% (45/175), 7 (4.0%) of which were early onset diarrhea and the rest 38 (21.7%) cases were delayed incidences. In terms of severity, 36 of the 45 cases (20.6%) were grade 1-2 diarrhea and 9 (5.1%) cases were grade 3-4 diarrhea. Notably, all of the grade 3-4 diarrhea were delayed diarrhea, which occurred after 5 to 14 days of medication. Age was a significant risk factor in patients 65 years old and above, who showed higher incidences of diarrhea (P=0.02). Combination chemotherapy with platinum also showed a statistically significant higher rate (17%, 8/47) of serious diarrhea than FOLFIRI regimen (P=0.003), but combination with oxaliplatin only showed a numerically higher while statistically insignificant incidence rate (40%, 4/10) of serious diarrhea (P=0.22). All the other clinical characteristics including gender, history of cigarette smoking and alcohol drinking, tumor type, dose of irinotecan and UGT1A1 gene polymorphism did not show any significant influence on the incidence or severity of diarrhea.CONCLUSION Diarrhea induced by irinotecan occurs at a higher risk in patients above or equal to 65, and intensive care should be taken to the occurrence of serious diarrhea with combination chemotherapy of irinotecan plus platinum.
伊立替康 / 化疗相关性腹泻 / 迟发性腹泻 / 危险因素 / UGT1A1基因多态性 {{custom_keyword}} /
irinotecan / chemotherapy induced diarrhea / delayed diarrhea / risk factors / UGT1A1 gene polymorphism {{custom_keyword}} /
[1] de Man FM, Goey AKL, van Schaik RHN, et al. Individualization of irinotecan treatment:A review of pharmacokinetics, pharmacodynamics, and pharmacogenetics. Clin Pharmacokinet, 2018, 57(10):1229-1254.
[2] Andreyev J, Ross P, Donnellan C, et al. Guidance on the management of diarrhoea during cancer chemotherapy. Lancet Oncol, 2014, 15(10):e447-460.
[3] YuQY, Wang HL, Wu T, et al. Acase of serious adverse effect induced by irinotecan. Chin Hosp Pharm J (中国医院药学杂志), 2012, 32(9):733-735.
[4] Cancer Therapy Evaluation Program. Common terminology criteria for adverse events, version 3.0(常规毒性判定标准3.0)[EB/OL]. (2003-03-21)[2006-08-09]. http://ctep.cancer.gov/protocoldevelopment/electronic-applications/docs/ctcaev3.pdf.
[5] Bleiberg H, Cvitkovic E. Characterisation and clinical management of CPT-11(irinotecan)-induced adverse events:the European perspective. Eur J Cancer, 1996, 32A Suppl 3:S18-23.
[6] Xu SZ. Clinical study on chemotherapy induced diarrhea in colorectal cancer patients[D]. Zhejiang University (浙江大学), 2014.
[7] Sun W, Yu ZT, Hu XW, et al. Progress in adverse effects and clinical intervention of irinotecan. Chin Pharm (中国药房), 2007, 18(35):2781-2783.
[8] Bano N, Najam R, Qazi F, et al. Gastrointestinal adverse effects in advanced colorectal carcinoma patients treated with different schedules of FOLFOX. Asian Pac J Cancer Prev, 2014, 15(19):8089-8093.
[9] Fukuda M, Nishio K, Kanzawa F, et al. Synergism between cisplatin and topoisomerase I inhibitors, NB-506 and SN-38, in human small cell lung cancer cells. Cancer Res, 1996, 56(4):789-793.
[10] Zhang XG, Zhang X. Analysis of 25 Cases of Adverse Reactions Induced by Inirotecan in Advanced Colorectal Cancer Patients. ChinJPharmacov (中国药物警戒), 2013, 10(3):168-171.
[11] Li H. Multiplevariate logistic analysis and model establishment of risk factors for irinotecan-induced adverse reaction[D]. Shandong University (山东大学), 2014.
[12] Alteration of the function of the UDP-glucuronosyltransferase 1A subfamily by cytochrome P4503A4:different susceptibility for UGT isoforms and UGT1A1/7 variants. Drug Metab Dispos, 2014, 42(2):229-238.
[13] Zheng JQ, Yang X, Wang Q, et al. Research progress in toxic effects of antitumor drugs based on drug transporter. Acta Pharm Sinica (药学学报), 2017, 52(10):1496-1504.
[14] Kweekel D,Guchelaar H J,Gelderblom H.Clinical and pharmacogenetic factors associated with irinotecan toxicity[J]. Cancer Treat Rev, 2008, 34(7):656-669.
[15] Wang WL, Zhu M, Guo DH, et al. Safety study on clinical application of irinotecan. Chin Pharmaceut (中国药业), 2011, 20(3):41-42.
[16] YangY, Gong XB, Liu K, et al. Detection and analysis on genepolymorphismsof UGT1A1*6 and UGT1A1*28 in 186 patients with digestive system malignant tumors. Chin Hosp Pharm J (中国医院药学杂志), 2018, 38(10):1077-1083.
[17] Cheng L, Li M, Hu J, et al. UGT1A1*6 polymorphisms are correlated with irinotecan-induced toxicity:a system review and meta-analysis in Asians. Cancer Chemother Pharmacol, 2014, 73(3):551-560.
[18] Hou HX, Qu YL, Tang XS, et al. Association of UGT1A1 polymorphisms with irinotecan-induced toxicities in advanced colorectal cancer:a meta-analysis in Asians. Chin J Cancer Prev Treat (中华肿瘤防治杂志), 2015, 22(20):1634-1640.
[19] Liu X, Cheng D, Kuang Q, et al. Association of UGT1A1*28 polymorphisms with irinotecan-induced toxicities in colorectal cancer:a meta-analysis in Caucasians. Pharmacogenomics J, 2014, 14(2):120-129.
[20] Lu YY, Huang XE, Wu XY, et al. Clinical observations on associations between the UGT1A1 genotype and severe toxicity of irinotecan. Asian Pac J Cancer Prev, 2014, 15(7):3335-3341.
[21] Wang Y, Yi C, Wang Y, et al. Distribution of uridine diphosphate glucuronosyltransferase 1A polymorphisms and their role in irinotecan-induced toxicity in patients with cancer. Oncol Lett, 2017, 14(5):5743-5752.
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