目的 观察局部进展或转移性结直肠癌患者化疗后,氟尿嘧啶(5-Fu)血药浓度与疗效及不良反应之间的关系,探讨其在进一步提高化疗疗效和减少不良反应中的作用.方法 86例不可切除的局部进展或转移性结直肠癌患者中,50例接受FOLFOX4方案(奥沙利铂+亚叶酸钙+氟尿嘧啶)、36例接受FOLFIRI方案(伊立替康+亚叶酸钙+氟尿嘧啶)一线化疗.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患者的5-Fu血药浓度.按照3个周期血药浓度的平均值,将86例患者分为＜ 25 ng/ml组、25 ～ 35 ng/ml组和＞35 ng/ml组,回顾性分析不同5-Fu血药浓度与化疗疗效和不良反应之间的关系.结果 ＜25 ng/ml组、25～ 35 ng/ml组和＞35 ng/ml组5-Fu血药浓度分别为(23.48±1.95) ng/ml、(31.47±2.33) ng/ml和(39.89±3.87) ng/ml,差异有统计学意义(P＜0.01).3组的疾病控制率(DCR)分别为61.5％、74.3％和80.0％,中位总生存期(OS)分别为13.0、18.0和17.5个月,中位无进展生存期(PFS)分别为4.5、7.5和8.0个月.与＜25 ng/ml组相比,25～35 ng/ml组和＞35 ng/ml组DCR分别提高了20.8％和30.1％,中位OS分别提高了5.0和4.5个月(P＜0.01),中位PFS分别提高了3.0和3.5个月(P＜0.01).随着5-Fu血药浓度的增高,化疗引起骨髓抑制、黏膜炎和腹泻的发生率增高,程度加重(P值分别为0.02、0.04和0.02).结论 晚期结直肠癌患者经过以5-Fu为基础的方案化疗后,5-Fu血药浓度在25～35 mg/L的患者预后较好,骨髓抑制、黏膜炎和腹泻等不良反应的发生率亦较低.%Objective To investigate the relationship between serum concentration of fluorouracil and therapeutic efficacy as well as adverse reactions in patients with unresectable locally advanced or measurable metastatic colorectal cancer,and to analyze its role in further improving therapeutic efficacy and reducing adverse reactions of fluorouracil-based chemotherapy.Methods Eighty-six patients were randomly assigned into three groups according to the average plasma concentration of fluorouracil after three cycles of chemotherapy with the initial regimen of two weeks FOLFOX-4 ( oxaliplatin + leucovorin + fluorouracil) or FOLFIRI (irinotecan + leucovorin + fluorouracil):group 1 (plasma concentration of fluorouracil ＜25 ng/ml),group 2 (25-35 ng/ml) and group 3 ( ＞35 ng/ml).The blood samples were taken at 12 h after continuous infusion of fluorouracil in each cycle and the plasma concentration of fluorouracil was detected by high performance liquid chromatography (HPLC) (about 5 am ± 1 h).The relationship between the drug plasma concentration,therapeutic efficacy and adverse reactions in different fluorouracil plasma concentration arms was analyzed retrospectively.Results The average plasma concentrations of fluorouracil of the three groups were (23.48 ± 1.95) ng/ml,(31.47 ± 2.33 ) ng/ml and (39.89 ± 3.87) ng/ml,respectively ( P ＜ 0.01 ).As for therapeutic efficacy,the median OS of the groups 2 and 3 were 18.0 and 17.5 months,significantly higher than that in the group 1 (13.0 months,P＜0.01).The PFS were 4.5,7.5 and 8.0 months,respectively ( P ＜ 0.01 ). In terms of adverse reactions,the incidences of bone marrow suppression,mucositis and diarrhea in the group 3 were significantly higher than that in the first two groups (P =0.02,P =0.04 and P =0.02).Conclusions The patients with local advanced and metastatic colorectal cancer,receiving fluorouracil-based chemotherapy,and with an average plasma concentration of fluorouracil between 25-35 mg/L have a better prognosis,and lower incidence of adverse reactions such as bone marrow suppression,mucositis and diarrhea.
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