日本甲状腺癌患者血浆中乐伐替尼和血管生成素浓度与乐伐替尼治疗临床反应之间的关联
Associations Between Plasma Concentrations of Lenvatinib and Angiopoietin and Clinical Responses to Lenvatinib Therapy in Japanese Patients With Thyroid Cancer.
作者信息
Kumagai Maho, Nagahama Mitsuji, Akamine Yumiko, Ozeki Tomoko, Suzuki Akifumi, Sugino Kiminori, Ito Koichi, Miura Masatomo
机构信息
Department of Pharmacy, Akita University Hospital, Akita, Japan.
Department of Surgery, Ito Hospital, Tokyo, Japan.
出版信息
Cancer Diagn Progn. 2022 May 3;2(3):336-344. doi: 10.21873/cdp.10114. eCollection 2022 May-Jun.
BACKGROUND/AIM: The purpose of this study was to investigate the relationships between the plasma concentration of Lenvatinib (C0), the levels of angiopoietin (Ang)-1 and Ang-2, and clinical responses to lenvatinib therapy in patients with thyroid cancer.
PATIENTS AND METHODS
Lenvatinib C and Ang were measured by high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively.
RESULTS
The median decrease rates of Ang-1 and Ang-2 at 1 month after treatment from baseline were -15.3% and -48.4%, respectively. However, the decrease in the levels of Ang-1 and Ang-2 at 1 month from baseline did not correlate with C0. In patients with partial response (PR) and stable disease, Ang-2 at 1 month was significantly lower than Ang-2 at baseline. The area under the ROC for PR prediction was 0.667, giving the best sensitivity (69.2%) and specificity (73.9%) at a threshold of decrease rate of Ang-2 of -49.83%.
CONCLUSION
The decrease in Ang-2 at 1 month of treatment from baseline may be important as a biomarker of the inhibitory effect of lenvatinib on angiogenesis.
背景/目的：本研究旨在探讨甲状腺癌患者中乐伐替尼的血浆浓度（C0）、血管生成素（Ang）-1和Ang-2水平与乐伐替尼治疗临床反应之间的关系。
患者与方法
分别采用高效液相色谱法和酶联免疫吸附测定法测量乐伐替尼C0和Ang。
结果
治疗1个月后，Ang-1和Ang-2相对于基线的中位下降率分别为-15.3%和-48.4%。然而，治疗1个月时Ang-1和Ang-2水平相对于基线的下降与C0无关。在部分缓解（PR）和疾病稳定的患者中，治疗1个月时的Ang-2显著低于基线时的Ang-2。PR预测的ROC曲线下面积为0.667，当Ang-2下降率阈值为-49.83%时，敏感性最佳（69.2%），特异性最佳（73.9%）。
结论
治疗1个月时相对于基线的Ang-2下降可能作为乐伐替尼对血管生成抑制作用的生物标志物具有重要意义。
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