氟尿嘧啶血药浓度监测在进一步提高晚期胃癌化疗疗效及减少不良反应预测中的作用  

The role of pharmacokinetic monitoring of fluorouracil in improvement of efficacy and reduction of adverse reactions for patients with advanced gastric cancer

作　　者：蔡讯[1] 薛鹏[1] 宋卫峰[1] 胡炯[1] 顾鸿莉[1] 杨海燕[1] 王理伟[1] 

机构地区：[1]上海交通大学附属第一人民医院肿瘤科,上海200080

出　　处：《肿瘤》2011年第10期930-936,共7页Tumor

摘　　要：目的:回顾性分析70例局部进展或转移性胃癌患者化疗后氟尿嘧啶(fluorouracil,5-FU)血药浓度与疗效及不良反应之间的关系,明确其在进一步提高疗效及减少不良反应中的作用。方法:70例不可切除局部进展或转移性胃癌患者随机接受多西他赛+顺铂+氟尿嘧啶(docetaxol+cisplatin+fluorouracil,DCF)或多西他赛+奥沙利铂+氟尿嘧啶(docetaxol+oxaliplatin+fluorouracil,DOF)3周方案化疗至少4个周期,于每周期5-FU持续滴注开始后12h应用高效液相色谱法检测5-FU血药浓度(检测时间控制在4～6AM)。分别取各周期血药浓度的平均值,通过逐步回归分析筛选与5-FU血药浓度相关的因素。再根据5-FU血药浓度有效预测可信区间分为≤25.5mg/L、25.6～37.4mg/L及>37.4mg/L3组,回顾性分析不同5-FU血药浓度与化疗疗效及不良反应之间的关系。结果:逐步回归分析提示,5-FU血药浓度与骨髓抑制、黏膜炎、无进展生存(progression-freesurvival,PFS)及总生存(overallsurvival,OS)相关,3组5-FU平均血药浓度分别为(20.73±3.80)mg/L、(31.98±3.10)mg/L和(40.32±3.45)mg/L(χ2=66.24,P<0.001),中位PFS分别为(4.50±0.19)(、6.00±0.32)和(7.50±0.75)个月(χ2=22.09,P<0.001),中位OS分别为(8.50±1.00)、(13.00±1.58)和(12.50±2.66)个月(χ2=32.32,P<0.001),第2、3组均明显高于第1组,第3组骨髓抑制和黏膜炎的发生率高于前两组(P=0.04和P=0.03)。结论:晚期胃癌患者在5-FU为基础的方案化疗后,5-FU血药浓度维持在25.6～37.4mg/L者能获得更好的生存,患者耐受性较好,骨髓抑制(尤其是Ⅲ/Ⅳ度)和黏膜炎等不良反应发生率亦较低。Objective： To retrospectively investigate the relationship between plasma concentration of fluorouracil and its therapeutic efficacy as well as adverse reactions in 70 patients with locally advanced or metastatic gastric cancer, and to determine the role of pharmacokinetic monitoring of fluorouracil in improvement of efficacy and reduction of adverse reactions of fluorouracil-based chemotherapy. Methods： Seventy patients with unresectable locally advanced or metastatic gastric cancer were randomly assigned into group A [treated with DCF regimen （docetaxol＋cisplatin＋fluorouracil）, repeated every three weeks for at least four cycles] and group B [treated with DOF regimen （docetaxol＋oxaliplatin＋fluorouracil）, repeated every three weeks for at least four cycles]. The plasma concentration of fluorouracil was detected by high performance liquid chromatography （HPLC） （time for detection： 4-6 AM） after continuous infusion of fluorouracil over 12 h in each cycle. The average value of plasma concentrations in each cycle was calculated, and the factors related to plasma concentration of fluorouracil were screened by stepwise regression. Then all patients were divided into three groups （group 1, group 2 and group 3） according to the predictive confidence interval of plasma fluorouracil concentration, and the average values of plasma fluorouracil concentration in each cycle of these three groups were less than or equal to 25.5 mg/L,25.6-37.4 mg/L, and more than 37.4 mg/L, respectively. The relationship between plasma concentration of fluorouracil and its therapeutic efficacy as well as adverse reactions was retrospectively analyzed. Results： Stepwise regression analysis showed that the plasma concentration of fluorouracil was associated with myelosuppression, mucositis, progression-free survival （PFS） and overall survival （OS）. The average plasma concentrations of fluorouracil in group 1, group 2 and group 3 were （20.73±3.80） mg/L, （31.98±3.10） mg/L and （40.32±3.45） m

关 键 词：胃肿瘤 血药浓度 氟尿嘧啶 药物监测 化疗反应 Kaplan—Meiers生存统计法 

分 类 号：R735.2[医药卫生—肿瘤]