摘要
背景与目的:5-氟尿嘧啶(5-FU)应用于不同的患者中,它的毒性及疗效均不同,个体差异较大。现发现二氢嘧啶脱氢酶(Dihydropyrimidinedehydrogenase,DPD)在其中起重要作用。本研究测定结直肠癌患者血DPD活性,并评价其与结直肠癌患者5-FU辅助化疗毒性及5-FU血药浓度之间的关系。方法:入选符合标准的结直肠癌患者30例,术前采用高效液相色谱法(HPLC)法测定血内源性二氢尿嘧啶(UH2)/尿嘧啶(U)值代表血DPD活性,术后2周行甲酰四氢叶酸(CF)60mg/m2,2h静脉滴注,5-FU425mg/m2,2h静脉滴注,连续5天方案,辅助化疗。第1天刚滴完5-FU时和第5天刚滴完5-FU时抽血查5-FU血药浓度。评价患者血DPD活性和患者5-FU化疗毒性及其与5-FU血药浓度之间的相关性。结果:30例结直肠癌患者行5-FU/CF方案辅助化疗。化疗前查血DPD活性为4.09±1.21,最低2.14,最高6.7,呈正态分布,个体差异较大。第1天刚滴完5-FU时5-FU血药浓度为(2079.12±621.41)μg/L(1200.10～3554.80μg/L);第5天刚滴完5-FU时5-FU血药浓度为(2197.64±606.78)μg/L(1259.00～3441.03μg/L),亦呈正态分布,个体差异较大。Pearson相关分析显示,血DPD活性与第1天刚滴完5-FU时5-FU血药浓度(r=-0.773,P=0.00)及第5天刚滴完5-FU时5-FU血药浓度(r=-0.833,P=0.00)呈负相关。t检验显?
BACKGROUND &OBJECTIVE: The efficacy and toxicity of 5-FU was va ri ous in different patients. It was reported that they were correlated to the acti vity of dihydropyrimidine dehydrogenase (DPD). This study is to measure DPD acti vity in blood and to analyze the relationship among DPD activity, the toxicity o f 5-FU based adjuvant chemotherapy and the 5-FU plasma concentration in colore ctal cancer patients. METHODS:30 colorectal cancer patients were enrolled into t he study to receive adjuvant chemotherapy 2 weeks after cured resection. The reg imen was 5-FU 425mg/m2 plus CF 60mg/m2 continuous infused for 2 hours, daily fo r 5 days. The concentration of endogenous uracil (U) and dihydrouracil (UH2) wer e assayed by high performance liquid chromatography (HPLC). The UH2-U ratio in plasma was used to represent DPD activity in blood. The plasma samples were coll ected before chemotherapy in all patients to detect the DPD activity in blood, a nd after 5-FU infusion at day1 and day5 to measure 5-FU plasma concentration. The relationship among the DPD activity in blood, the toxicity of chemotherapy a nd the plasma concentration of 5-FU in all patients were analyzed. RESULTS: 30 colorectal cancer patients have received adjuvant chemotherapy. The DPD activity in the blood of 30 colorectal cancer patients before chemotherapy was 4.09±1.2 1 (2.14-6.7), showed a trend of normal distribution. The 5-FU plasma concentra tion after 5-FU infusion was (2 079.12±621.41) 靏/L (1 200.10-3 554.80 靏/L ) at the first day, and (2 197.64靏/L at the fifth day (1 259.00-3 4 41.03 靏/L). There was a negative relationship between the DPD activity in bloo d and the 5-FU plasma concentration at day1 (r=-0.773,P=0.00), and day5 after 5-FU infusion(r=-0.833,P=0.00). No significant difference between the 5-FU plasma concentration of day1 and day5 was found (P=0.458). The 5-Fu associated toxicities had a negative relationship with DPD activity in blood, and had a pos itive relationship with 5-FU plasma concentration (P< 0.05). CONCLUSION:The res ults indicated that the DPD activity in blood can be used to predict the toxicit y and the 5-FU plasma concentration in patients with 5-FU based chemotherapy.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2004年第z1期1512-1516,共5页
Chinese Journal of Cancer
关键词
二氢嘧啶脱氢酶
尿嘧啶
二氢尿嘧啶
结直肠肿瘤
辅助化疗
Dehydropyrimidine dihydrogenase
Uracil
Dihydrouracil
Colorectal ne oplasms
Adjuvant chemotherapy
