结直肠癌患者DPD水平与5-FU血药浓度、疗效及毒性的相关性研究  

Relationship of Serum Level of Dihydropyrimidine Dehydrogenase and Serum Concentration of 5-Fluorouracil to Treatment Response and Adverse Events in Colorectal Cancer Patients

作　　者：董秋美[1] 何友兼[1] 李苏[1] 周中梅[1] 张力[1] 周志伟[2] 夏忠军[1] 李玉颜[1] 

机构地区：[1]中山大学肿瘤防治中心内科,广东广州510060 [2]中山大学肿瘤防治中心腹科,广东广州510060

出　　处：《癌症》2005年第4期483-487,共5页Chinese Journal of Cancer

摘　　要：背景与目的:以相同的FOLFOX6方案治疗晚期结直肠癌患者,疗效和不良反应却明显不同。二氢嘧啶脱氢酶(DPD)是影响5鄄FU化疗疗效及不良反应的主要因素之一。本研究主要探讨结直肠癌患者外周血DPD水平与标准FOLFOX6方案治疗后患者5鄄FU血药浓度、不良反应及疗效的相关性。方法:应用高效液相色谱法(HPLC)检测结直肠癌患者化疗前DPD水平,按标准的FOLFOX6方案给药后,检测5鄄FU稳态血药浓度(HPLC法),同时观察化疗不良反应和疗效。结果:DPD在72例结直肠癌患者中呈正态分布,从1.55～5.94不等;5鄄FU稳态血药浓度在结直肠癌患者之间具有较大的变异,从141.1μg/L到1741.9μg/L,不呈正态分布。DPD水平和5鄄FU血药浓度呈负相关(r=-0.460,P<0.01),5鄄FU血药浓度≤600μg/L时不良反应较小,>600μg/L时不良反应明显增加,差异具有显著性(P<0.05)。不同治疗反应组的平均血药浓度之间差异具有显著性(P<0.05)。DPD水平和口腔粘膜炎、腹泻等具有相关性,DPD水平和疗效没有相关性(r=0.312,P=0.078)。结论:DPD水平和5鄄FU稳态血药浓度在结直肠癌患者之间具有较大的差异。DPD水平和5鄄FU血药浓度及毒性呈负相关,5鄄FU稳态血药浓度和不良反应以及治疗反应呈正相关。BACKGROUND & OBJECTIVE: Toxicities and response are different when pa tients with advanced colorectal cancer were treated with standard FOLFOX6 regime n. Serum level of dihydropyrimidine dehydrogenase (DPD) relates to efficacy and toxicities of chemotherapy containing 5-fluorouracil (5-FU). This study was to e xplore relationship of DPD to serum concentration of 5-FU in colorectal cancer p atients treated with FOLFOX6 regimen, and their correlation to treatment respons e and adverse events. METHODS: Serum level of DPD in 72 patients with colorectal cancer was detected by high-performance liquid chromatography (HPLC) before che motherapy. Serum concentration of 5-FU at steady state was detected by HPLC afte r patients received FOLFOX6 regimen. Treatment response and adverse events in th e patients were assessed. RESULTS: Serum levels of DPD were normally distributed in 72 patients (ranged 1.55-5.94), while serum concentrations of 5-FU at steady state were not (ranged 141.1-1 741.9 μg/L). Serum level of DPD was negatively correlated with serum concentration of 5-FU (r=-0.460, P < 0.01). Occurrence of adverse events was lower when 5-FU concentration was less than 600 μg/L than wh en 5-FU concentration was more than 600 μg/L (P < 0.05). The mean serum concent ration of 5-FU was significantly higher in patients with complete response and p artial response than in patients with steady disease, and progressive disease (5 13.9 μg/L vs. 409.8 μg/L, and 259.3 μg/L, P < 0.05). Serum level of DPD was l ower in patients suffered oral mucositis and diarrhea of grade Ⅱ-Ⅳ than in pat ients suffered oral mucositis and diarrhea of grade 0-Ⅰ (P=0.016, P=0.047). Ser um level of DPD had no relation with treatment response of the patients (r=0.312 , P=0.078). CONCLUSIONS: DPD level and serum 5-FU concentration vary a lot among patients with colorectal cancer. DPD level negatively correlates with serum 5-F U concentration. Serum concentration of 5-FU correlates with treatment effect an d toxicities.

关 键 词：结直肠肿瘤 5-氟尿嘧啶 二氢嘧啶脱氢酶 稳态血药浓度 高效液相色谱法 疗效 

分 类 号：R735.3[医药卫生—肿瘤]