肾衰竭对乳腺癌患者多西他赛暴露和不良反应的影响

Effect of renal failure on docetaxel exposure and adverse reactions in breast cancer patients

目的探讨肾衰竭对乳腺癌患者多西他赛的药时曲线下面积(AUC)和不良反应是否有影响,以便对此类患者的多西他赛用药提供依据。方法采用回顾性研究方法,选择2019年1月至2021年11月我院收治的24例已行乳腺癌根治术的使用AC-T辅助化疗的乳腺癌患者。根据肾功能病例分为两组,肾衰竭组5例、肾功能正常组19例。收集两组患者的临床特征,包括性别、年龄、体重、体表面积;多西他赛使用剂量、血药浓度、药时曲线下面积;化疗前患者肝肾功能、白细胞计数及中性粒细胞绝对值。采用单因素线性回归分析多西他赛AUC的影响因素。收集患者使用多西他赛化疗后的不良反应:恶心呕吐、骨髓抑制、便秘及肝功能损伤。以CTCAE 4.0评价标准进行不良反应评价。结果肾功能衰竭组与肾功能正常组的临床特征:肌酐[908.0(819.0,1018.0)μmol/L、54.8(52.0,65.0)μmol/L]、肌酐清除率[4.9(4.3,5.4)ml/min、86.3(59.3,92.5)ml/min],差异有统计学意义(P<0.001)。其他临床特征:体表面积[1.4(1.4,1.5)m^(2)、1.6(1.5,1.6)m^(2)]、多西他赛给药剂量[70.4(69.4,73.0)mg/m^(2)、74.4(72.3,91.2)mg/m^(2)]、体重[(51.4±3.8)kg、(51.5±5.5)kg],差异均无统计学意义(P>0.05)。多西他赛化疗前肝功能及白细胞、中性粒细胞绝对值均在正常范围内。两组患者使用多西他赛后AUC值[(1.6±0.6)mg·h/L、(1.8±0.8)mg·h/L]差异无统计学意义(P>0.05)。多西他赛AUC的线性单因素回归分析显示多西他赛滴注结束时的血药浓度与其有显著相关性(P<0.001),而其患者体表面积、多西他赛给药剂量、体重、肝肾功能均与多西他赛AUC无相关性(P>0.05)。多西他赛化疗后两组患者不良反应:恶心呕吐(I度发生率:40%、57.9%,II度发生率:60%、42.1%)、骨髓抑制(I度发生率:60%、84.2%,II度发生率:20%、15.8%)、便秘(均出现轻度便秘)的发生率差异均无统计学意义(P>0.05)。结论肾功能衰竭并不影响乳腺癌患者多西他赛的暴露及使用多西他赛后出现的不良反应。

Objective To investigate the influence of renal failure on the area under curve(AUC)and adverse reactions of docetaxel in breast cancer patients,and provide evidence for the dosage of docetaxel in renal failure patients.Methods A retrospective study was conducted on 24 patients with breast cancer who had undergone radical mastectomy and received AC-T adjuvant chemotherapy in our hospital from January 2019 to November 2021.According to renal function cases,the patients were divided into two groups:renal failure group(n=5)and normal renal function group(n=19).The clinical characteristics such as gender,age,body weight and body surface area of patients in two groups,docetaxel dose,blood concentration,area under the curve,liver and kidney function,white blood cell count and absolute value of neutrophil before chemotherapy were collected.Single factor linear regression was used to analyze the influencing factors of the AUC of docetaxel.Adverse reactions after chemotherapy with docetaxel including nausea and vomiting,bone marrow suppression,constipation and liver function injury were collected.CTCAE 4.0 evaluation standard was used to evaluate adverse reactions.Results The clinical characteristics of creatinine[908.0(819.0,1018.0)μmol/L vs 54.8(52.0,65.0)μmol/L]and creatinine clearance rate[4.9(4.3,5.4)ml/min vs 86.3(59.3,92.5)ml/min]of the renal failure group and the normal renal function group have significant difference(P<0.001),while no significant difference(P>0.05)were found in the body surface area[1.4(1.4,1.5)m^(2)vs 1.6(1.5,1.6)m^(2)],docetaxel dose[70.4(69.4,73.0)mg/m^(2)vs 74.4(72.3,91.2)mg/m^(2)],body weight[(51.4±3.8)kg vs(51.5±5.5)kg].Liver function,white blood cells and neutrophils were within the normal range before chemotherapy with docetaxel.There was no significant difference in AUC value[(1.6±0.6)mg·h/L vs(1.8±0.8)mg·h/L]between the two groups after chemotherapy with docetaxel(P>0.05).Linear univariate regression analysis indicated that the blood concentration at the end of docetaxel infusion was significantly associated with AUC of docetaxel(P<0.001),while the body surface area,dose of docetaxel,body weight,liver and kidney function were not correlated with AUC of docetaxel(P>0.05).After chemotherapy with docetaxel,adverse reactions of patients in the two groups:nausea and vomiting(grade I incidence:40%vs.57.9%,grade II incidence:60%vs.42.1%),myelosuppression(grade I incidence:60%vs.84.2%,grade II incidence:20%vs 15.8%)and constipation(all mild constipation)had no significant difference(P>0.05).Conclusion Renal failure did not affect the exposure of docetaxel and the adverse reactions after chemotherapy with docetaxel in breast cancer patients.