Death Caused by Degree-Ⅳ Myelosuppression after Oral Tegafur, Gimeracil and Oteracil Potassium Capsule: a Report of One Case and the Literature Review_West China Medical Journal

Authors：

 YuLijuan ,  FengLingling

Department of Clinical Pharmacy, Kaifeng Central Hospital, Kaifeng, Henan 475001, P. R. China;

Corresponding author：

FengLingling, Email: fll57@163.com

Keywords：

Myelosuppression; Tegafur, gimeracil and oteracil potassium; Individualized administration; Dihydropyrimidine dehydragenase gene detection

DOI：

10.7507/1002-0179.201600465

Video：

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Objective To suggest the importance of taking notice of oral chemotherapy drugs in cancer patients, and the importance of drug-use evaluation in patients with insufficient kidney functions, by reporting one death case caused by multiple organ failure because of myelosuppression after oral tegafur, gimeracil and oteracil potassium (S-1) capsules for 10 days in a patient with insufficient kidney functions. Methods Through the analysis of one patient who died of multiple organ failure due to degree-Ⅳ myelosuppression and the related literature review, we discussed the necessity of individualized administration of clinical chemotherapy. Results The patient had grade-Ⅱ renal insufficiency before chemotherapy and did not undergo dihydropyrimidine dehydrogenase (DPYD) gene test. Myelosuppression occurred 10 days after oral chemotherapy drugs. The white blood cells, neutrophils and platelets decreased progressively, and then developed into degree-Ⅳ suppression. Finally the patient died of multiple organ failure. Conclusion s Genetic variation and renal insufficiency may cause differences in drug metabolism. The reduced urinary excretion of guimet pyrimidine (CDHP), the inhibitors of dihydropyrimidine dehydrogenase which is the 5-fluorouracil (5-FU) metabolic enzyme, may lead to elevated plasma concentration of 5-FU, thereby increasing myelosuppression and other adverse reactions. If DPYD gene detection results show low enzyme activity, it can cause lethal toxicity through deceleration of 5-FU metabolism and high concentration of blood. DPYD gene dzetection should be performed if allowed, and individualized treatment plan should be formulated after comprehensive evaluation. The overall situation of the patients should be considered before treatment, and then individualized drugs should be administered.

Citation： YuLijuan, FengLingling. Death Caused by Degree-Ⅳ Myelosuppression after Oral Tegafur, Gimeracil and Oteracil Potassium Capsule: a Report of One Case and the Literature Review. West China Medical Journal, 2016, 31(10): 1689-1692. doi: 10.7507/1002-0179.201600465 Copy

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11.	徐皖湘, 陈振东.二氢嘧啶脱氢酶活性在食管癌5-FU化疗中的应用价值[J].安徽医科大学学报, 2007, 42(1): 84-86.
12.	章宏, 厉有名, 虞朝辉, 等.肿瘤患者二氢嘧啶脱氢酶基因多态性与5-氟尿嘧啶毒副反应的关系[J].中华内科杂志, 2007, 46(2): 103-106.
13.	王勇, 徐曦, 王慧.结直肠癌患者DPYD基因多态性与5-FU毒性反应相关的Meta分析[J].山东医药, 2014, 54(41): 18-21.
14.	刘洋, 刘华, 吕娟丽, 等.医院2010年-2013年抗菌药物不良反应分析[J].中华医院感染学杂志, 2014, 24(6): 1370-1371, 1374.
15.	何忠芳, 郑茂华, 武新安, 等.哌拉西林钠他唑巴坦钠致白细胞减少[J].药物不良反应杂志, 2012, 14(5): 308-309.
16.	杨媛, 张威, 毛璐, 等.哌拉西林钠他唑巴坦钠致白细胞减少的临床特征分析[J].中国医院药学杂志, 2014, 34(7): 550-552.
17.	李琦恒, 倪鸿昌.亚胺培南/西司他丁不良反应回顾性调查分析[J].中国药物应用与监测, 2010, 7(4): 223-225.
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1. Kunisaki C, Takahashi M, Makino HA, et al. Phase Ⅱ study of biweekly docetaxel and S-1 combination chemotherapy as first-line treatment for advanced gastric cancer[J]. Cancer Chemother Pharmacol, 2011, 67(6): 1363-1368.
2. Jeung HC, Rha SY, Im CK, et al. A randomized phase 2 study of docetaxel and S-1 versus docetaxel and cisplatin in advanced gastric cancer with an evaluation of SPARC expression for personalized therapy[J]. Cancer, 2011, 117(10): 2050-2057.
3. 张鹏, 成健, 李新梅.替吉奥联合胸腔化疗治疗老年非小细胞肺癌合并胸腔积液临床疗效观察[J].中国医学工程, 2013, 20(9): 14-15.
4. 王洪云, 疏云, 吴燕玲, 等.三维适形放疗辅助替吉奥治疗老年中晚期食管癌的可行性及安全性研究[J].中国当代医药, 2014, 21(26): 45-47.
5. 万学红, 卢雪峰.诊断学[M]. 8版.北京:人民卫生出版社, 2013: 344.
6. 王传新, 王谦.检验与临床诊断-肾病分册[M].北京:人民军医出版社, 2006: 287-289.
7. Fleming RA, Milano G, Thyss A, et al. Correlation between dihydropyrimidine dehydrogenase activity in peripheral mononuclear cells and systemic clearance of fluorouracil in cancer patients[J]. Cancer Res, 1992, 52(10): 2899-2902.
8. Liu XQ, Zhuang M, Wang Z, et al. Correlation between dihydropyrimidine dehydrogenase and efficacy and toxicity of fluoropyrimidine drugs[J]. Eur Rev Med Pharmacol Sci, 2014, 18(18): 2772-2776.
9. Iyer SN, Singhal RS, Hegde MR, et al. Genetic variation in dihydropyrimidine dehydrogenase (DPYD) gene in a healthy adult Indian population[J]. Ann Hum Biol, 2015, 42(1): 97-100.
10. Froehlich TK, Amstutz U, Aebi S, et al. Clinical importance of risk variants in the dihydropyrimidine dehydrogenase gene for the prediction of early-onset fluoropyrimidine toxicity[J]. Int J Cancer, 2015, 136(3): 730-739.
11. 徐皖湘, 陈振东.二氢嘧啶脱氢酶活性在食管癌5-FU化疗中的应用价值[J].安徽医科大学学报, 2007, 42(1): 84-86.
12. 章宏, 厉有名, 虞朝辉, 等.肿瘤患者二氢嘧啶脱氢酶基因多态性与5-氟尿嘧啶毒副反应的关系[J].中华内科杂志, 2007, 46(2): 103-106.
13. 王勇, 徐曦, 王慧.结直肠癌患者DPYD基因多态性与5-FU毒性反应相关的Meta分析[J].山东医药, 2014, 54(41): 18-21.
14. 刘洋, 刘华, 吕娟丽, 等.医院2010年-2013年抗菌药物不良反应分析[J].中华医院感染学杂志, 2014, 24(6): 1370-1371, 1374.
15. 何忠芳, 郑茂华, 武新安, 等.哌拉西林钠他唑巴坦钠致白细胞减少[J].药物不良反应杂志, 2012, 14(5): 308-309.
16. 杨媛, 张威, 毛璐, 等.哌拉西林钠他唑巴坦钠致白细胞减少的临床特征分析[J].中国医院药学杂志, 2014, 34(7): 550-552.
17. 李琦恒, 倪鸿昌.亚胺培南/西司他丁不良反应回顾性调查分析[J].中国药物应用与监测, 2010, 7(4): 223-225.
18. 周践, 周筱青. 65例亚胺培南/西司他丁药品不良反应分析[J].中华医院感染学杂志, 2004, 14(6): 671-673.

West China Medical Journal

Death Caused by Degree-Ⅳ Myelosuppression after Oral Tegafur, Gimeracil and Oteracil Potassium Capsule: a Report of One Case and the Literature Review

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