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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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, 陳振東.二氫嘧啶脫氫酶活性在食管癌5-FU化療中的應用價值[J].安徽醫科大學學報, 2007, 42(1): 84-86.
12.	章宏, 厲有名, 虞朝輝, 等.腫瘤患者二氫嘧啶脫氫酶基因多態性與5-氟尿嘧啶毒副反應的關系[J].中華內科雜志, 2007, 46(2): 103-106.
13.	王勇, 徐曦, 王慧.結直腸癌患者DPYD基因多態性與5-FU毒性反應相關的Meta分析[J].山東醫藥, 2014, 54(41): 18-21.
14.	劉洋, 劉華, 呂娟麗, 等.醫院2010年-2013年抗菌藥物不良反應分析[J].中華醫院感染學雜志, 2014, 24(6): 1370-1371, 1374.
15.	何忠芳, 鄭茂華, 武新安, 等.哌拉西林鈉他唑巴坦鈉致白細胞減少[J].藥物不良反應雜志, 2012, 14(5): 308-309.
16.	楊媛, 張威, 毛璐, 等.哌拉西林鈉他唑巴坦鈉致白細胞減少的臨床特征分析[J].中國醫院藥學雜志, 2014, 34(7): 550-552.
17.	李琦恒, 倪鴻昌.亞胺培南/西司他丁不良反應回顧性調查分析[J].中國藥物應用與監測, 2010, 7(4): 223-225.
18.	周踐, 周筱青. 65例亞胺培南/西司他丁藥品不良反應分析[J].中華醫院感染學雜志, 2004, 14(6): 671-673.

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. 張鵬, 成健, 李新梅.替吉奧聯合胸腔化療治療老年非小細胞肺癌合并胸腔積液臨床療效觀察[J].中國醫學工程, 2013, 20(9): 14-15.
4. 王洪云, 疏云, 吳燕玲, 等.三維適形放療輔助替吉奧治療老年中晚期食管癌的可行性及安全性研究[J].中國當代醫藥, 2014, 21(26): 45-47.
5. 萬學紅, 盧雪峰.診斷學[M]. 8版.北京:人民衛生出版社, 2013: 344.
6. 王傳新, 王謙.檢驗與臨床診斷-腎病分冊[M].北京:人民軍醫出版社, 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, 陳振東.二氫嘧啶脫氫酶活性在食管癌5-FU化療中的應用價值[J].安徽醫科大學學報, 2007, 42(1): 84-86.
12. 章宏, 厲有名, 虞朝輝, 等.腫瘤患者二氫嘧啶脫氫酶基因多態性與5-氟尿嘧啶毒副反應的關系[J].中華內科雜志, 2007, 46(2): 103-106.
13. 王勇, 徐曦, 王慧.結直腸癌患者DPYD基因多態性與5-FU毒性反應相關的Meta分析[J].山東醫藥, 2014, 54(41): 18-21.
14. 劉洋, 劉華, 呂娟麗, 等.醫院2010年-2013年抗菌藥物不良反應分析[J].中華醫院感染學雜志, 2014, 24(6): 1370-1371, 1374.
15. 何忠芳, 鄭茂華, 武新安, 等.哌拉西林鈉他唑巴坦鈉致白細胞減少[J].藥物不良反應雜志, 2012, 14(5): 308-309.
16. 楊媛, 張威, 毛璐, 等.哌拉西林鈉他唑巴坦鈉致白細胞減少的臨床特征分析[J].中國醫院藥學雜志, 2014, 34(7): 550-552.
17. 李琦恒, 倪鴻昌.亞胺培南/西司他丁不良反應回顧性調查分析[J].中國藥物應用與監測, 2010, 7(4): 223-225.
18. 周踐, 周筱青. 65例亞胺培南/西司他丁藥品不良反應分析[J].中華醫院感染學雜志, 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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