肾癌术后患者5-氟尿嘧啶血药浓度与肾功能及毒副作用的相关性研究

Correlation of Plasma Concentration of 5-fluorouracil with Renal Function and Adverse Effects of 5-fluorouracil-based Chemotherapy in Patients with Radical Surgery for Renal Cell Carcinoma

目的探讨肾癌术后患者5-氟尿嘧啶(5-FU)血药浓度与肾功能、毒副作用的关系,为实施个体化治疗提供依据。方法选取2013年8月—2016年2月在海南省人民医院泌尿外科行肾癌根治性切除术患者92例为研究对象,均给予基于5-FU的综合化疗,共4个疗程。检测化疗后5-FU血药浓度与肾功能指标尿素氮(BUN)、肌酐(Cr)水平,采用WHO毒性分级标准评价骨髓抑制、胃肠道反应、手足综合征、口腔黏膜炎等毒副作用的严重程度。根据5-FU血药浓度,将患者分为<300.0μg/L组(42例)和≥300.0μg/L组(50例)。结果 92例患者5-FU血药浓度为179.2~1 589.6μg/L,平均(569.5±29.5)μg/L。≥300.0μg/L组血清BUN、Cr水平均高于<300.0μg/L组,骨髓抑制、胃肠道反应、手足综合征、口腔黏膜炎等毒副作用严重程度均高于<300.0μg/L组(P<0.05)。5-FU血药浓度与BUN、Cr水平呈正相关(r=0.413,P=0.008;r=0.398,P=0.010)。结论肾癌术后患者5-FU血药浓度变异性较大,5-FU血药浓度过高可导致肾功能异常,加重毒副作用,临床可通过监测5-FU血药浓度为实施个体化治疗提供依据。

Objective To investigate the correlation of plasma concentration of 5-fluorouracil（ 5-FU） with renal function and adverse effects of 5-FU-based chemotherapy in patients with radical surgery for renal cell carcinoma,so as to provide a reference for developing individualized treatment for these patients. Methods We enrolled 92 consecutive cases of renal cell carcinoma who received radical surgery and four cycles of 5-FU-based comprehensive chemotherapy from August 2013 to February 2016. The measurement of plasma concentration of 5-FU and levels of renal function markers,such as BUN and Cr was performed after the chemotherapy. Patients who had plasma concentration of 5-FU 300. 0 μg/L and ≥300. 0 μg/L were assigned to 300. 0 μg/L group（ n = 42） and ≥300. 0 μg/L（ n = 50） group,respectively. The WHO Toxicity Grading Scale for Determining the Severity of Adverse Events was used to assess the severity of adverse effects of the chemotherapy,such as myelosuppression,gastrointestinal reactions,hand-foot syndrome,and oral mucositis. Results The plasma concentration of5-FU in all the participants ranged from 179. 2 μg/L to 1 589. 6 μg/L,averaged（ 569. 5 ± 29. 5） μg/L. Compared with those in the 300. 0 μg/L group,patients in the ≥300. 0 μg/L group had much higher levels of serum BUN and Cr,and they were more serious on myelosuppression,gastrointestinal reactions,hand-foot syndrome,and oral mucositis（ P〈0. 05）. Pearson correlation analysis showed that the BUN and Cr levels increased with the plasma concentration of 5-FU（ r = 0. 413,P = 0. 008;r = 0. 398,P = 0. 010）. Conclusion The plasma concentration of 5-FU varies greatly in patients with radical surgery for renal cell carcinoma receiving 5-FU-based chemotherapy. Excessive high plasma concentration of 5-FU can lead to abnormal renal function and aggravate the adverse effects of the chemotherapy. Therefore,the plasma concentration of 5-FU can be used as a reference for developing individualized treatment for such patients.