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5-氟尿嘧啶和多西紫杉醇稳态血药浓度影响化疗不良反应及近期疗效

Effects of Stability Plasma Concentration of 5-Fu and Docetaxel on Adverse Events and Short Term Effect after 5-Fu and Docetaxel Chemotherapy

  • 摘要: 目的 回顾性分析5-氟尿嘧啶(5-fluorouracil,5-Fu)和多西紫杉醇(Docetaxel,DOC)稳态血药浓度与联合化疗毒性反应和近期疗效的相关性。方法 用5-Fu联合DOC方案(5-Fu 2.5 g/m2 维持静脉滴注120 h,亚叶酸钙 0.2 g,d1~5,DOC 75 mg/m2,d1,21天重复)化疗的胃癌或食管癌患者40例,采用高效液相色谱法分别测定化疗后5-Fu和DOC稳态血药浓度。采用Fisher精确概率法分析5-Fu和DOC稳态血药浓度和化疗不良反应及近期疗效的相关性。结果 5-Fu稳态血药浓度个体间变异较大,血药浓度范围为1.2~96.6 mg/L;DOC血药浓度范围为0.34~0.98 mg/L。按5-Fu血药浓度<30 mg/L和≥30 mg/L将患者分为两组,两组之间腹泻、黏膜炎严重程度差异有统计学意义,但近期疗效差异无统计学意义;按DOC血药浓度<4.9 mg/L和≥4.9 mg/L分为两组,高浓度组患者骨髓抑制程度及临床疗效均明显高于低浓度组。结论 相同体表面积剂量下5-Fu和DOC联合化疗后稳态血药浓度个体间存在显著差异,稳态浓度影响了联合化疗后毒性反应的严重程度及近期疗效,提示进行血药浓度监测可以预测化疗毒性及疗效。

     

    Abstract: Objective To analyse the relationship between stability plasma concentration of 5-Fu, docetaxel and adverse effects, short term effect. Methods Forty patients with gastic cancer or esophageal caner received the same regimen (continuous infusion of 5-Fu 2.5g/m2 for 120 h, leucovorin 200 mg d1-5 and paclitaxel 75mg /m2 d1 every three weeks).The stability concentrations of 5-Fu and docetaxel were detected by high-performance liquid chromatography (HPLC).The relationship between stability plasma concentration of 5-Fu,docetaxel and adverse effects, short term effect was analysed with Fisher's exact test. Results The interindividual variation of 5-Fu stability plasma concentration was large.The concentration of 5-Fu varied from 1.2 mg/L to 99.6 mg/L,and docetaxel varied from 0.34 mg/L to 0.98 mg/L,which were demonstrated normalitydistribution.Patients were grouped in to two groups which were 5-Fu concentration <30 mg/L and ≥30 mg/L, the degree of diarrhea and mucositis had obvious difference between the two groups, while short term effect had no difference. When the two groups were divided by docetaxel concentration <4.9mg/L and ≥4.9 mg/L, patients with high concentration docetaxel had more severe myelosupression and better short term effect. Conclusion The stability concentration of 5-Fu and docetaxel had large interindividual variability after chemotherapy according to body surface area. The stability concentration effected the adverse events and short term effect. Mornitoring plasma concentration of chemotherapeutics may predict the toxicity and effect.

     

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