多西他赛治疗非小细胞肺癌的时辰药理学研究

Chronopharmacology of Docetaxel in the Treatment of Non-Small Cell Lung Cancer

关键词:  多西他赛  时辰药理学  非小细胞肺癌

Key words:  docetaxel  chronopharmacology  NSCLC

摘要:

目的 比较多西他赛在不同时间点给药后的血药浓度、疗效以及毒性反应的变化，根据其节律变化选择临床最佳给药时间，获得最佳疗效。方法 经病理和细胞学证实的60例III、IV期非小细胞肺癌(NSCLC)患者随机分为3组。多西他赛：A组(n=20)在8∶00 am给药，B组(n=20)在2∶00 pm给药，C组(n=20)在8∶00 pm给药；顺铂在多西他赛给药后第2天给予。多西他赛40 mg·m^-2，ivgtt，d1，8；顺铂75 mg·m^-2，ivgtt，d1，第21天重复。测定给药后1，10，24 h的血药浓度，并评价经化疗2个周期后的疗效和不良反应。结果 3组的疗效和血药浓度在统计学上没有显著性差异，但2:00 pm，8:00 pm给药组的不良反应发生率较高。结论 多西他赛治疗NSCLC在8∶00 am给药较为安全有效，可增加病例数做进一步的深入研究。

Abstract:

OBJECTIVE To evaluate the concentration, efficacy and toxicity of docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC) by administration at different times. METHODS Sixty patients with locally advanced or metastatic NSCLC were enrolled into the study and divided to three groups. Each group were administrated of docetaxel at different time. A: administration at 8∶00 am (n=20), B: administration at 2∶00 pm (n=20), C: administration at 8∶00 pm (n=20)；cisplatin was administered at second day. Docetaxel 40 mg·m^-2, ivgtt, d1, 8; cisplatin 75 mg·m^-2, ivgtt, d1, every 21 days. HPLC was established for the determination of docetaxel at 1, 10, 24 h after administration, and evaluate the efficacy and toxicity after two cycles. RESULTS There was no statistic difference, but the main toxicities of B, C groups were higher. CONCLUSION A group is a better method for the treatment of NSCLC with mild toxicity and appropriate, it can be recommended for further clinical trail.