检测多西他赛血药浓度指导晚期非小细胞#br# 肺癌患者的个体化治疗#br# #br#

目的观察多西他赛（DTX）治疗晚期非小细胞肺癌（NSCLC）根据血药浓度调整剂量对疗效及不良反应的影响。 方法收集2015年10月至2017年4月晚期NSCLC患者100例，一线予以DTX联合卡铂方案化疗。第1周期DTX剂量为75 mg／m2，后根据所得的血浆浓度与时间曲线下面积（AUC）及是否存在骨髓抑制进行分组。AUC在25～37 mg·h／L的患者分入常规组；＜25 mg·h／L或＞37 mg·h／L且存在骨髓抑制者分入试验组。常规组DTX剂量在后续周期中均按75 mg／m2给予。试验组后续周期中DTX剂量需根据上一周期AUC水平及骨髓抑制的程度在上周期DTX剂量基础上进行调整。 结果常规组（n=50）获 PR 16例，SD 21例，PD 13例；有效率（RR）为320％，疾病控制率（DCR）为740％；中位无进展生存时间（PFS）为55个月。试验组（n=50）获PR 19例，SD18例，PD13例；RR为380％，DCR为740％；中位PFS为58个月。两组RR、DCR和中位PFS的差异均无统计学意义（P＞005）。常规组4个周期AUC的均值差异较小，波动于31～33（mg·h／L），仅2例患者第4周期因骨髓抑制DTX减量25％。试验组第2周期35例患者DTX减量15％，8例患者减量25％，7例患者减量30％；第3周期5例患者减量15％，1例患者减量25％。随着DTX剂量的调整，AUC均值也随之减低，第4周期AUC均值低于常规组（30 mg·h/L vs. 33 mg·h/L， P＜005）。常规组骨髓抑制的比例随着化疗周期数的增加而增高，而试验组骨髓抑制的比例随着化疗周期数的增加及AUC值的降低而减低，第4周期试验组骨髓抑制的发生率远低于常规组（162％ vs. 649％，P＜0001）。 结论通过血药浓度调整DTX剂量治疗NSCLC，疗效与常规给药方法相当，不良反应减轻，值得临床推广应用。

Individualization treatment of docetaxel by detecting plasma concentration in advanced non small cell lung cancer#br#

ObjectiveTo explore the changes in the efficacy and adverse events of docetaxel （DTX） after adjusting dose according to the plasma concentration in advanced non small cell lung cancer（NSCLC）. MethodsA total of 100 advanced NSCLC patients from October 2015 to April 2017 were enrolled and given DTX+carboplatin regimen as the first line chemotherapy. The dose of DTX for the first cycle was 75 mg／m2， and then patients were divided into conventional group and experimental group according to area under the plasma drug concentrations time curve （AUC） and the degree of myelosuppression. Patients of AUC ranging from 25 to 37 mg·h／L were assigned into conventional group， and patients of AUC ＜25 or ＞37 mg·h／L and myelosuppression were assigned to experimental group. The DTX dose in conventional group was given at 75 mg／m2 in subsequent cycles. And the dose in experimental group was adjusted according to the AUC and the degree of myelosuppression in the previous cycle. ResultsIn conventional group， there were 16 cases in PR， 21 cases in SD， and 13 cases in PD. The response rate （RR） was 320％， the disease control rate was 740％， and the median progression free survival（PFS） was 55 months. In experimental group， there were 19 cases in PR， 18 cases in SD， and 13 cases in PD. The RR and DCR were 380％ and 740％， and the median PFS was 58 months. The differences of RR， DCR and median PFS between the two groups had no differences （P＞005）. The average AUC ranged 31 33（mg·h／L） in conventional group. The dose of DTX was reduced by 25％ due to myelosuppression in 2 patients at the fourth cycle. In experimental group， 35 patients had 15％ DTX dose reduction， 8 patients had 20％ reduction and 7 patients had 30％ reduction at the second cycle； 5 patients had 15％ reduction and 1 patient had 25％ reduction at the third cycle. With the adjustment of DTX， the average of AUC decreased. The average AUC at the fourth cycle was 30， lower than 33 of conventional group （P＜005）. The occurrence of myelosuppression in conventional group rose with the increase of chemotherapy cycles， while that in experimental group decreased with the increase of chemotherapy cycles and decrease of AUC. The occurrence of myelosuppression in experimental group was 162％， much lower than 649％ of conventional group （P＜0001）. ConclusionBy adjusting the DTX dose based on plasma concentration for NSCLC， the efficacy is equal to conventional treatment with less adverse events， which is worthy of clinical application.