晚期结直肠癌患者氟尿嘧啶剂量与血药浓度和生存的关系

The relationship between the dose of fluorouracil and its plasma concentration and the survival of patients with advanced colorectal cancer

目的：探讨接受以5-氟尿嘧啶（5-fluorouracil，5-FU）为基础的-线、二线化疗方案的晚期结直肠癌患者的5-FU给药剂量（基于或不基于体表面积计算）与5-FU血药浓度和生存之间的关系。方法：192例晚期结直肠癌患者接受以5-FU为基础的FOLFOX（5-FU、亚叶酸钙和奥沙利铂）和FOLFIRI（5-FU、亚叶酸钙和伊立替康）方案作为一线和二线化疗（或相反顺序）。治疗过程中，依据患者的不良反应调整5-FU剂量，同时检测5-FU的稳态血药浓度。结果：5-FU的血药浓度与持续输注剂量无关（r=0.066，P=0.146），与基于体表面积计算的持续输注剂量也无关（r=0.056，P=0.217）。高5-FU血药浓度组（〉30μg／L）患者的中位生存时间为31.4个月，低5-FU血药浓度组（〈30μg／L）患者的中位生存时间为14.5个月（P=0.001）。在高5-FU血药浓度组中，3～4级中性粒细胞减少和手足综合征更常见。结论：5-FU血药浓度监测对晚期结直肠癌患者可能是-种确定5-FU安全有效剂量的依据之-。

Objective： To investigate the relationship between 5-FU （5-fluorouracil） dose （based on body surface area or not） and its plasma concentration and the overall survival of patients with advanced colorectal cancer receiving 5-FU-based chemotherapy regimens as standard first- and second-line treatment. Methods： One hundred and ninety-two patients with advanced colorectal cancer received 5-FU-based chemotherapy regimens of FOLFOX （5-FU, calcium folinate and oxaliplatin） and FOLFIRI （5-FU, calcium folinate and irinotecan ） as first-line and second-line chemotherapy, respectively or in a reverse sequence. Plasma concentration of 5-FU at steady state was examined when the dose of 5-FU was adjusted according to the toxicity in each patient. Results： The plasma concentration of 5-FU was not associated with the dose of continuous infusion of 5-FU （r = 0.066, P = 0.146）, and also not associated with the dose of infusional 5-FU based on body surface area （r = 0.056, P = 0.21 7）. Median overall survival was 31.4 months for patients with high plasma concentration of 5-FU （〉 30 μg/L） versus 14.5 months for patients with low plasma concentration of 5-FU （〈 30 μg/L） （P = 0.001）. The adverse effects including grades 3-4 neutropenia and hand foot syndrome were more frequent in patients with high plasma concentration of 5-FU. Conclusion： The monitoring of plasma concentration of 5-FU may be a basis for dose adjustment of 5-FU in safe and effective range for patients with advanced colorectal cancer.