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乳腺癌患者多西他赛药时曲线下面积与中性粒细胞减少的相关性

Relationship Between Docetaxel AUC and Neutropenia in Patients with Breast Cancer

  • 摘要:
    目的 研究乳腺癌患者化疗后,多西他赛(docetaxel, DTX)药时曲线下面积(area under curve, AUC)与血液学毒性(中性粒细胞减少)的相关性,为患者个体化给药提供理论依据。
    方法 选择郑州大学附属肿瘤医院2016年12月—2017年7月接受AC序贯T化疗方案的94例乳腺癌患者,采用胶乳免疫比浊法测定患者静脉输注DTX后的血药浓度,并通过非混合效应模型软件计算多西他赛AUC。建立利用AUC预测化疗后中性粒细胞减少百分比的数学模型。
    结果 多西他赛AUC在(0.7~3.9)mg·h/L之间,平均值为(2.34±0.7)mg·h/L,患者间AUC的变异系数(CV%)为30%。出现低级别(0~2级)及高级别(3~4)中性粒细胞减少的AUC平均值分别为2.29 mg·h/L和2.82 mg·h/L(P=0.003)。利用多西他赛AUC预测中性粒细胞减少百分比的模型为y=-1.8672x2+25.658x-14.92, r=0.643。
    结论 本研究建立的利用AUC预测中性粒细胞减少百分比的数学模型,为通过测定患者AUC进行多西他赛个体化的给药提供了理论依据。

     

    Abstract:
    Objective To investigate the relationship between docetaxel AUC(area under curve) and neutropenia in patients with breast cancer after chemotherapy.
    Methods We selected 94 patients with breast cancer who accepted AC sequential T chemotherapy regimen as the first-line treatment from December 2016 to July 2017 in the Affiliated Cancer Hospital of Zhengzhou University. The plasma concentration of docetaxel was detected by latex immunoturbidimetry after the docetaxel continuous infusion. Docetaxel AUC was calculated using nonparametric mixed-effects models. A mathematical model predicting decreased percentage of neutrophils using docetaxel AUC was established.
    Results Individual exposure to docetaxel was highly variable (AUC range=0.7-3.9 mg·h/L, mean value=(2.34±0.7)mg·h/L, inter-individual CV=30%). The average AUC for low (0-2) and high grade (3-4) neutropenia were 2.29 and 2.82 mg·h/L, respectively(P=0.003). The model predicting decreased percentage of neutrophils using docetaxel AUC was set as y=-1.8672x2+25.658x-14.92, r=0.643.
    Conclusion This research set up a mathematical model to predict decreased percentage of neutrophil, which provide basis for screening high-risk patients who may suffer seriously hematological toxicity and lay a theoretical foundation for individualized dosage based on docetaxel AUC.

     

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