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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 AND AIM: The efficacy and side effects of adverse reactions were significantly different in patients with advanced colorectal cancer treated with the same FOLFOX6 regimen. Dihydropyrimidine dehydrogenase (DPD) is one of the main factors affecting the efficacy and side effects of 5-FU chemotherapy. The aim of this study is to investigate the correlation between peripheral blood DPD levels in patients with colorectal cancer and the 5-FU blood concentration, adverse reactions, and efficacy of the standard FOLFOX6 regimen. Methods: The levels of DPD in patients with colorectal cancer before chemotherapy were determined by high performance liquid chromatography (HPLC). After the standard FOLFOX6 regimen was given, 5-FU steady-state blood concentration (HPLC method) was measured. Adverse reactions of chemotherapy and Efficacy. Results: DPD showed a normal distribution in 72 patients with colorectal cancer, ranging from 1.55 to 5.94. The 5-FU steady-state plasma concentration had a significant variation in patients with colorectal cancer, ranging from 141.1 μg / L to 1741.9μg / L, not normal distribution. The level of DPD was negatively correlated with the concentration of 5-FU (r = -0.460, P <0.01). The adverse reactions of 5-FU with the concentration of less than 600μg / L were small and the adverse reaction was significantly increased when> 600μg / Significant (P <0.05). The mean plasma concentrations of different treatment response groups were significantly different (P <0.05). There was no correlation between DPD level and oral mucositis and diarrhea. The correlation between DPD level and curative effect was not significant (r = 0.312, P = 0.078). Conclusion: There is a great difference between DPD level and 5-FU steady-state plasma concentration in patients with colorectal cancer. DPD levels and 5-FU blood concentration and toxicity was negatively correlated, 5-FU steady-state plasma concentration and adverse reactions and treatment response was positively correlated.