Clinical Value of Pharmacokinetic Monitoring of Serum Paclitaxel Concentration in Paclitaxel-based Chemotherapy on Patients with Ovarian Cancer
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摘要:目的
研究卵巢癌患者化疗后，紫杉醇（PTX）血药浓度与疗效及不良反应的相关性。
方法75例卵巢癌患者接受PT方案（紫杉醇+卡铂）一线化疗。于每周期PTX静脉输注开始后（24±6）h采集静脉血2次，采用胶乳免疫比浊法检测PTX浓度。根据PTX血药浓度的平均值，将75例患者分为≤25 h组、（26~30）h组和≥31 h组，回顾性分析PTX血药浓度与疗效及与不良反应间的相关性。
结果≤25 h组、（26~30）h组、≥31 h组PTX血药浓度分别为（22.54±2.04）h、（28.62±1.87）h、（33.01±2.84）h，差异有统计学意义（P < 0.05）。随着PTX血药浓度的升高，化疗的不良反应发生率增多，程度加强（P < 0.05）。（26~30）h组的有效率（31.25%）高于≤25 h组（20%）（P=0.02），与≥31 h组有效率（33.33%）相比差异无统计学意义（P=0.96）。
结论卵巢癌采用紫杉醇PTX血药浓度在（26~30）h的患者疗效好，且不良反应稍低。
Abstract:ObjectiveTo investigate the relationship between plasma concentration of paclitaxel (PTX) and the efficacy as well as toxic and side effects in the patients with ovarian cancer.
MethodsSeventy-five patients with ovarian cancer accepted PT (paclitaxel+carboplatin) chemotherapy regimen as their first line treatment. The blood samples were taken twice at (24±6) h after continuous infusion of paclitaxel in each cycle and the plasma concentration of paclitaxel was detected by latex immuno-turdidimetry. The patients were randomly assigned into three groups according to the average plasma concentration of paclitaxel: group 1 (plasma concentration paclitaxel≤25h), group 2(26-30h) and group 3(≥31h). The relationship between the drug plasma concentration, therapeutic efficacy and adverse reactions in different paclitaxel plasma concentration was analyzed retrospectively.
ResultsThe average plasma concentrations of paclitaxel of the three groups were (22.54±2.04) h, (28.62±1.87) h, 33.01±2.84) h, respectively (P < 0.05). The incidence and extent of adverse reactions were significantly higher and stronger with the increasing plasma concentration of paclitaxel. The therapeutic efficacy of group 2 (26-30) h was 31.25% which was better than that (20%) of group 1 (≤25h) (P=0.02), but had no significant difference with that (33.33%) of group 3 (≥31h) (P=0.96).
ConclusionThe ovarian cancer patients treated with paclitaxel-based chemotherapy with an average plasma concentration of paclitaxel between 26-30h have a higher curative effect and lower toxic side effect.
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Key words:
- Ovarian cancer /
- Paclitaxel /
- Plasma concentration /
- Latex immuno-turdidimetry
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图 2 基于BSA给药的不同患者PTX血药浓度（Tc > 0.05）的分布
Figure 2 The distribution of PTX blood concentration (Tc > 0.05) in different patients based on BSA administration
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图 3 基于BSA给药的卵巢癌患者PTX浓度与白细胞减少的相关性
Figure 3 The correlation between PTX concentration and leukopenia in ovarian cancer patients based on BSA administration
表 1 患者各时间点药物浓度
Table 1 Concentration of PTX in patients' blood (μmol/L) at different timepoints
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表 2 不同患者紫杉醇临界0.05 μmol/L血药浓度以上暴露时间
Table 2 Exposure time of blood concentration above 0.05μmol/L in different patients
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表 3 不同PTX血药浓度的卵巢癌患者的临床特征比较
Table 3 The clinical features of ovarian cancer patients with different PTX concentration
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表 4 三组不同PTX血药浓度患者的不良反应比较 (n)
Table 4 The toxic side effect in three patients' groups with different PTX concentrations (n)
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表 5 三组不同PTX浓度患者的疗效比较 (n)
Table 5 The curative effect in three patients' groups with different PTX concentrations (n)
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[1] 刘晋雯.紫杉醇联合顺铂、卡铂周疗治疗卵巢癌疗效及安全评价[J].中国保健营养 (中旬刊), 2012, 6(6): 326. http://www.cnki.com.cn/Article/CJFDTOTAL-NMYZ201503034.htm Liu JW. The curative effect and safety evaluation of Paclitaxel combined Cisplatin or Carboplatin in weekly chemotherapy on ovarian cancer[J]. Zhongguo Bao Jian Yin Yang (Zhong Xun Kan), 2012, 6(6): 326. http://www.cnki.com.cn/Article/CJFDTOTAL-NMYZ201503034.htm
[2] Hendrikx JJ, Hillebrand MJ, Thijssen B, et al. A sensitive combined assay for the quantification of paclitaxel, docetaxel and ritonavir in human plasma using liquid chromatography coupled with tandem mass spectrometry[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2011, 879(28): 2984-90. doi: 10.1016/j.jchromb.2011.08.034
[3] 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): 372-4, 385. Dong BH, Sun PM, Song YY, et al. Determination of Paclitaxel in Ovarian Neoplasm Patients' Plasma by HPLC[J]. Guo Ji Fu Chan Ke Xue Za Zhi, 2013, 40(4): 372-4, 385.
[4] 叶怀庄, 方维佳, 徐农.高效液相色谱法在肿瘤化疗患者紫杉醇血药浓度检测中的应用[J].中华检验医学杂志, 2009, 32(2): 198-200. http://cdmd.cnki.com.cn/Article/CDMD-10570-1011304580.htm Ye HZ, Fang WJ, Xu N. Determination of chemotherapy drug in cancer patients' plasma by High performance liquid chromatography (HPLC)[J]. Zhonghua Jian Yan Yi Xue Za Zhi, 2009, 32(2): 198-200. http://cdmd.cnki.com.cn/Article/CDMD-10570-1011304580.htm
[5] 蔡讯, 薛鹏, 宋卫峰, 等.氟尿嘧啶血药浓度监测在进一步提高晚期结直肠癌以氟尿嘧啶为基础的化疗疗效中的作用[J].中华肿瘤杂志, 2012, 34(1): 39-43. http://www.cnki.com.cn/Article/CJFDTOTAL-ZZLL201110011.htm Cai X, Xue P, Song WF, et al. Role of pharmacokinetic monitoring of serum fluorouracil concentration in patients with local advanced and metastatic colorectal cancer and further improving efficacy of fluorouracil-based chemotherapy[J]. Zhonghua Zhong Liu Za Zhi, 2012, 34(1): 39-43. http://www.cnki.com.cn/Article/CJFDTOTAL-ZZLL201110011.htm
[6] Wang N, He T, Shen Y, et al. Paclitaxel and Tacrolimus Coencapsulated Polymeric Micelles That Enhance the Therapeutic Effect of Drug-Resistant Ovarian Cancer[J]. ACS Appl Mater Interfaces, 2016, 8(7): 4368-77. doi: 10.1021/acsami.5b09340
[7] 邹厚文, 罗会俊, 余瑛, 等.紫杉醇联合顺铂的两种给药方法治疗晚期卵巢癌疗效的比较[J].江西医药, 2014, 49(3): 232-4. http://www.cnki.com.cn/Article/CJFDTOTAL-JXYY201403023.htm Zou HW, Luo HJ, Yu Y, et al. The curative effect comparison of Paclitaxel combined Cisplatin in two administration modes on advanced ovarian cancer[J]. Jiangxi Yi Yao, 2014, 49(3): 232-4. http://www.cnki.com.cn/Article/CJFDTOTAL-JXYY201403023.htm
[8] Wang B, Li S, Meng X, et al. Inhibition of mdr1 by G-quadruplex oligonucleotides and reversal of paclitaxel resistance in human ovarian cancer cells[J]. Tumor Biol, 2015, 36(8): 6433-43. doi: 10.1007/s13277-015-3333-2
[9] 杨建伟, 苏颖, 陈增, 等. CYP3A4基因多态性与晚期胃癌患者接受紫杉醇/奥沙利铂多线化疗、化疗周期数及不良反应的相关性[J].国际病理科学与临床杂志, 2014, 34(1): 22-8. http://www.cnki.com.cn/Article/CJFDTOTAL-WYSB201401005.htm Yang JW, Su Y, Chen Z, et al. Correlation between gene polymorphisms of CYP3A4 and multi-line chemotherapy, cycles of chemotherapy or adverse reactions in gastric cancer patients received therapy of paclitaxel and/or oxaliplatin combination regimens[J]. Guo Ji Bing Li Ke Xue Yu Lin Chuang Za Zhi, 2014, 34(1): 22-8. http://www.cnki.com.cn/Article/CJFDTOTAL-WYSB201401005.htm
[10] 杨建伟, 陈增, 苏颖, 等.胃癌细胞色素氧化酶CYP3A4基因多态性与含紫杉醇方案化疗敏感性的研究[J].临床肿瘤学杂志, 2014, 19(1): 23-8. http://www.cnki.com.cn/Article/CJFDTOTAL-LCZL201401005.htm Yang JW, Chen Z, Su Y, et al. Trial of the correlation between cytochrome oxidase CYP3A4 with the susceptibility of paclitaxel-based regimen for advanced gastric cancer[J]. Lin Chuang Zhong Liu Xue Za Zhi, 2014, 19(1): 23-8. http://www.cnki.com.cn/Article/CJFDTOTAL-LCZL201401005.htm
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