紫杉醇脂质体药代动力学参数T_(c>0.05)在肺癌化疗中应用
|
摘要
目的探讨在肺癌联合化疗过程中,紫杉醇脂质体药代动力学参数Tc> 0. 05与肺癌化疗近期肿瘤指标之间的相关性;并探究Tc> 0. 05值与肺癌化疗后副反应的相关性。方法选取14例病理学确诊的肺癌患者。所有患者接受紫杉醇脂质体联合卡铂的化疗方案,采用胶乳免疫比浊法检测患者血浆中紫杉醇脂质体的浓度,并应用紫杉醇脂质体群体药代动力学模型计算软件推算出Tc> 0. 05。通过病案记录采集病人信息,探讨Tc> 0. 05及紫杉醇脂质体血药浓度和化疗近期肿瘤指标的关系,以及与毒副反应的相关性。结果 Tc> 0. 05在化疗近期肿瘤指标变化上无明显统计学差异(P> 0. 05)。最常见的副反应白细胞下降Ⅰ-Ⅱ度和Ⅲ-Ⅳ度与Tc> 0. 05值有统计学差异(P <0. 05),Ⅲ-Ⅳ度白细胞下降患者所测Tc> 0. 05值高于Ⅰ-Ⅱ度白细胞下降者Tc> 0. 05值。结论紫杉醇脂质体药动参数Tc> 0. 05值与肺癌患者近期肿瘤指标相关性不显著。紫杉醇脂质体联合化疗最常见的副反应中,Tc> 0. 05值越高,患者越倾向于出现白细胞Ⅲ-Ⅳ度下降。
Objective To investigate the correlation between liposomal paclitaxel pharmacokinetic parameters Tc > 0. 05 and short-term tumor markers response for patients with lung cancer who accepted L-PTX-based chemotherapy,and to explore the correlation between Tc > 0. 05 and side effect of chemotherapy. Methods Patients with histologically or cytologically confirmed lung cancer were enrolled into this study. All patients enrolled eceived L-PTX +carboplatin( CBP). It used latex immune turbidimetric method to detect paclitaxel liposome in plasma concentrations,and paclitaxel liposome population pharmacokinetic model calculation software to calculate Tc > 0. 05. Demographic characteristics,clinicopathologic characteristics and laboratory indexes were recorded according to medical records,and the relationship between the blood concentration of Tc > 0. 05 and L-PTX and the recent tumor indexes of chemotherapy was analyzed,as well as the correlation with the toxic and side effects. Results There was no statistically significant difference in the recent tumor markers between chemotherapy and Tc > 0. 05( P > 0. 05). The most common side effect were white blood cell decline,Ⅰ-Ⅱ degree and Ⅲ-Ⅳ degree,and the Tc > 0. 05 value was statistically different( P < 0. 05). The Tc > 0. 05 value of patients with Ⅲ-Ⅳ white blood cell decline was higher than that of Ⅰ-Ⅱ,and the Tc > 0. 05 value of WBC decreased. Conclusion Tc > 0. 05 suggests to be no correlated with short-term tumor markers response for L-PTX based chemotherapy in treating patients with lung camcer,but it is found to be significantly increased in patients with grade Ⅲ-Ⅳ Leukocyte depletion.
Objective To investigate the correlation between liposomal paclitaxel pharmacokinetic parameters Tc > 0. 05 and short-term tumor markers response for patients with lung cancer who accepted L-PTX-based chemotherapy,and to explore the correlation between Tc > 0. 05 and side effect of chemotherapy. Methods Patients with histologically or cytologically confirmed lung cancer were enrolled into this study. All patients enrolled eceived L-PTX +carboplatin( CBP). It used latex immune turbidimetric method to detect paclitaxel liposome in plasma concentrations,and paclitaxel liposome population pharmacokinetic model calculation software to calculate Tc > 0. 05. Demographic characteristics,clinicopathologic characteristics and laboratory indexes were recorded according to medical records,and the relationship between the blood concentration of Tc > 0. 05 and L-PTX and the recent tumor indexes of chemotherapy was analyzed,as well as the correlation with the toxic and side effects. Results There was no statistically significant difference in the recent tumor markers between chemotherapy and Tc > 0. 05( P > 0. 05). The most common side effect were white blood cell decline,Ⅰ-Ⅱ degree and Ⅲ-Ⅳ degree,and the Tc > 0. 05 value was statistically different( P < 0. 05). The Tc > 0. 05 value of patients with Ⅲ-Ⅳ white blood cell decline was higher than that of Ⅰ-Ⅱ,and the Tc > 0. 05 value of WBC decreased. Conclusion Tc > 0. 05 suggests to be no correlated with short-term tumor markers response for L-PTX based chemotherapy in treating patients with lung camcer,but it is found to be significantly increased in patients with grade Ⅲ-Ⅳ Leukocyte depletion.
引文
[1]胡毅,陶海涛.晚期非小细胞肺癌的药物治疗进展[J].中国药物应用与监测,2014,11(6):329-333.
[2]陈颖波,陈嘉,张莉莉,等.国产紫杉醇脂质体治疗非小细胞肺癌和乳腺癌的Ⅲ期临床试验报告[J].现代肿瘤医学,2007,15(5):708-710.
[3]闫伟.紫杉醇脂质体辅助治疗乳腺癌的安全性和有效性[J].海峡药学,2013,25(2):79-80.
[4]杨华.紫杉醇脂质体联合顺铂治疗老年中晚期肺鳞癌的疗效及安全性评价[J].中国医药指南,2017,15(29):100-101.
[5]顾海娟,郭小红,朱冬梅,等.卵巢癌患者代谢酶基因多态性与紫杉醇血药浓度及不良反应的相关性[J].中华实用诊断与治疗杂志,2012,26(12):1185-1187.
[6]冯桂阳.紫杉醇脂质体单药与紫杉醇脂质体联合顺铂治疗肺癌的疗效分析[J].中国民康医学,2017,29(15):40-42.
[7]杨新杰,张卉,农靖颖,等.紫杉醇脂质体联合顺铂方案一线治疗晚期非小细胞肺癌的临床随机对照研究[J].中国肺癌杂志,2012,15(4):208-212.
[8]李秋萍,王卫.脂质体紫杉醇联合奈达铂与紫杉醇联合奈达铂一线治疗晚期非小细胞肺癌的临床观察[J].中南医学科学杂志,2017,45(5):513-515.
[9] WANG H,CHENG G,DU Y,et al. Hypersensitivity reaction studies of a polyethoxylated castor oil-free,liposome-based alternative paclitaxel formulation[J]. Mol Med Rep,2013,7(3):947-952.
[10]钱俐,繆捷飞,茅国新.紫杉醇脂质体联合卡铂治疗老年晚期非小细胞肺癌的疗效观察[J].中国肿瘤临床与康复,2013,20(7):741-743.
[11]盛华明.紫杉醇脂质体联合卡铂治疗非小细胞肺癌的临床疗效观察[J].中国医疗前沿,2012,7(19):41-42.
[12] QI W X,SHEN Z,LIN F,et al. Paclitaxel-based versus docetaxelbased regimens in metastatic breast cancer:A systematic review and meta-analysis of randomized controlled trials[J]. Curr Med Res Opin,2013,29(2):117-125.
[13]付莹,陈道礼,张大昕.血清肿瘤标记物在肺癌复发及预后中的临床意义[J/OL].中华临床医师杂志(电子版),2012,6(14):4082-4084[2018-04-28]. http://med. wanfangdata. com.cn/Paper/Detail? id=Periodical Paper_zhlcyszz201214067&dbid=WF_QK. DOI:10. 3877/cma. j. issn. 1674-0785. 2012. 14.065.
[14]李立军,刘利,李猛,等.血清CEA、CA199、CYFRA21-1、SCC、NSE、TK1水平联合检测在肺癌复发中的诊断价值分析[J].临床合理用药杂志,2015,8(34):127-128.
[15]董滨华,孙蓬明,宋一一,等.高效液相色谱法测定卵巢癌患者血浆中紫杉醇浓度的研究[J].国际妇产科学杂志,2013,40(4):372-374,385.
[16]钟皎,赵文艳,王丽萍.高效液相色谱法测定非小细胞肺癌患者血浆中紫杉醇浓度[J].中国医院药学杂志,2008,28(7):538-540.
[17] JOERGER M,KRAFF S,HUITEMA A D,et al. Evaluation of a pharmacology-driven dosing algorithm of 3-weekly paclitaxel using therapeutic drug monitoring:A pharmacokinetic-pharmacodynamic simulation study[J]. Clin Pharmacokinet,2012,51(9):607-617.
[2]陈颖波,陈嘉,张莉莉,等.国产紫杉醇脂质体治疗非小细胞肺癌和乳腺癌的Ⅲ期临床试验报告[J].现代肿瘤医学,2007,15(5):708-710.
[3]闫伟.紫杉醇脂质体辅助治疗乳腺癌的安全性和有效性[J].海峡药学,2013,25(2):79-80.
[4]杨华.紫杉醇脂质体联合顺铂治疗老年中晚期肺鳞癌的疗效及安全性评价[J].中国医药指南,2017,15(29):100-101.
[5]顾海娟,郭小红,朱冬梅,等.卵巢癌患者代谢酶基因多态性与紫杉醇血药浓度及不良反应的相关性[J].中华实用诊断与治疗杂志,2012,26(12):1185-1187.
[6]冯桂阳.紫杉醇脂质体单药与紫杉醇脂质体联合顺铂治疗肺癌的疗效分析[J].中国民康医学,2017,29(15):40-42.
[7]杨新杰,张卉,农靖颖,等.紫杉醇脂质体联合顺铂方案一线治疗晚期非小细胞肺癌的临床随机对照研究[J].中国肺癌杂志,2012,15(4):208-212.
[8]李秋萍,王卫.脂质体紫杉醇联合奈达铂与紫杉醇联合奈达铂一线治疗晚期非小细胞肺癌的临床观察[J].中南医学科学杂志,2017,45(5):513-515.
[9] WANG H,CHENG G,DU Y,et al. Hypersensitivity reaction studies of a polyethoxylated castor oil-free,liposome-based alternative paclitaxel formulation[J]. Mol Med Rep,2013,7(3):947-952.
[10]钱俐,繆捷飞,茅国新.紫杉醇脂质体联合卡铂治疗老年晚期非小细胞肺癌的疗效观察[J].中国肿瘤临床与康复,2013,20(7):741-743.
[11]盛华明.紫杉醇脂质体联合卡铂治疗非小细胞肺癌的临床疗效观察[J].中国医疗前沿,2012,7(19):41-42.
[12] QI W X,SHEN Z,LIN F,et al. Paclitaxel-based versus docetaxelbased regimens in metastatic breast cancer:A systematic review and meta-analysis of randomized controlled trials[J]. Curr Med Res Opin,2013,29(2):117-125.
[13]付莹,陈道礼,张大昕.血清肿瘤标记物在肺癌复发及预后中的临床意义[J/OL].中华临床医师杂志(电子版),2012,6(14):4082-4084[2018-04-28]. http://med. wanfangdata. com.cn/Paper/Detail? id=Periodical Paper_zhlcyszz201214067&dbid=WF_QK. DOI:10. 3877/cma. j. issn. 1674-0785. 2012. 14.065.
[14]李立军,刘利,李猛,等.血清CEA、CA199、CYFRA21-1、SCC、NSE、TK1水平联合检测在肺癌复发中的诊断价值分析[J].临床合理用药杂志,2015,8(34):127-128.
[15]董滨华,孙蓬明,宋一一,等.高效液相色谱法测定卵巢癌患者血浆中紫杉醇浓度的研究[J].国际妇产科学杂志,2013,40(4):372-374,385.
[16]钟皎,赵文艳,王丽萍.高效液相色谱法测定非小细胞肺癌患者血浆中紫杉醇浓度[J].中国医院药学杂志,2008,28(7):538-540.
[17] JOERGER M,KRAFF S,HUITEMA A D,et al. Evaluation of a pharmacology-driven dosing algorithm of 3-weekly paclitaxel using therapeutic drug monitoring:A pharmacokinetic-pharmacodynamic simulation study[J]. Clin Pharmacokinet,2012,51(9):607-617.