鼻咽癌患者5-FU血药浓度与毒性及疗效的关系

背景与目的:5-氟尿嘧啶(5-fluorouracil,5-FU)对人体的作用有几条途径,不同个体对5-FU的代谢有很大的差异,故很难预测5-FU对不同个体的治疗效果和毒副作用。本研究拟探讨5-FU的稳态血药浓度在接受相同初始剂量(按体表面积计算)的患者之间的差异,以及其与不良反应、治疗反应之间的关系。方法:在接受顺铂(cisplatin,DDP)联合5-FU连续静脉灌注治疗的20例鼻咽癌患者中,开始5-FU治疗后24h采集血样,用高效液相色谱仪(HPLC)测定5-FU的血药浓度。HPLC条件:1mmol/L磷酸盐缓冲液作为流动相,流速1.3ml/min,波长260nm,柱温25℃。结果:5-FU血药浓度在鼻咽癌患者中呈正态分布,个体间有明显差异。5-FU血药浓度低于600μg/L时,患者均没有不良反应,而高于1000μg/L时,患者均出现较严重的不良反应。不同级别不良反应及不同的治疗反应所对应的5-FU血药浓度之间存在明显的统计学差异(P<0.05)。结论:5-FU血药浓度在接受相同初始剂量(按体表面积计算)的患者之间存在明显的差异。5-FU血药浓度与其毒副作用、治疗反应有关。

Relationship of plasma concentration of 5-fluorouracil with toxicity and response in patients with nasopharyngeal carcinoma

BACKGROUND & OBJECTIVE: Because there are several mechanisms of activity and toxicity and inter-individual variation in pharmaco- dynamics of 5-fluorouracil (5-FU),it is difficult to predict the sensitivity and toxicity of 5-FU in an individual patient. This study was designed to assess inter-patient variation of 5-FU steady-state plasma concentration and the relationship of plasma concentration of 5-FU with toxic side effects and therapeutic response. METHODS: Twenty patients with nasopharyngeal carcinoma were treated with 5-FU combined with cisplatin(DDP).Blood samples were collected after 24 hours of infusion of 5-FU. Plasma concentrations of 5-FU were measured using high performance liquid chromatography(HPLC) with column temperature at 25 Celsius degree, flow rate at 1.3 ml/min, wave length at 260 nm and 1 mmol/l phosphate buffer (pH 3.0) as mobile phase. RESULTS: The plasma concentrations of 5-FU were normally distributed in the patients. No adverse effects were noted in the patients with plasma concentration of 5-FU lower than 600 microg/L, and severe toxic side effects were observed in the patients with plasma concentration of 5-FU greater than 1000 microg/L.The differences between plasma concentrations of 5-FU and each grade side effects reached statistical significance (P< 0.05). CONCLUSION: The plasma concentration of 5-FU have highly inter-individual variation in the patients with nasopharyngeal carcinoma. Plasma concentrations of 5-FU were associated with the toxicity and treatment response.