李田源, 海龙, 吴慧, 洪锡田, 卢晓旭, 孙学明. 阿帕替尼治疗耐药的复发胶质母细胞瘤的临床研究[J]. 中国肿瘤临床, 2021, 48(12): 619-623. DOI: 10.3969/j.issn.1000-8179.2021.12.207
引用本文: 李田源, 海龙, 吴慧, 洪锡田, 卢晓旭, 孙学明. 阿帕替尼治疗耐药的复发胶质母细胞瘤的临床研究[J]. 中国肿瘤临床, 2021, 48(12): 619-623. DOI: 10.3969/j.issn.1000-8179.2021.12.207
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Tianyuan Li, Long Hai, Hui Wu, Xitian Hong, Xiaoxu Lu, Xueming Sun. Clinical research of apatinib in the treatment of durg-resistant recurrent glioblastoma[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2021, 48(12): 619-623. DOI: 10.3969/j.issn.1000-8179.2021.12.207
Citation: Tianyuan Li, Long Hai, Hui Wu, Xitian Hong, Xiaoxu Lu, Xueming Sun. Clinical research of apatinib in the treatment of durg-resistant recurrent glioblastoma[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2021, 48(12): 619-623. DOI: 10.3969/j.issn.1000-8179.2021.12.207
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阿帕替尼治疗耐药的复发胶质母细胞瘤的临床研究

Clinical research of apatinib in the treatment of durg-resistant recurrent glioblastoma

    摘要
  • 摘要:
      目的  探讨阿帕替尼治疗替莫唑胺（temozolomide，TMZ）耐药的复发胶质母细胞瘤（glioblastoma，GBM）的疗效和不良反应，并观察治疗过程中免疫因子的变化。
      方法  选取2018年7月至2020年10月郑州大学附属肿瘤医院标准方案治疗失败的GBM患者51例，给予阿帕替尼和TMZ治疗。阿帕替尼500 mg/d口服，第1～14天；休息7天，开始口服TMZ 150 mg/（m2·d），连续口服5天，28天为1个周期。连续服用直至疾病进展或不可耐受。治疗前及治疗后每周采集外周血，采用ELISA法检测外周血中可溶性PD-1（soluble programmed death-1，sPD-1）、可溶性PD-L1（soluble programmed death-ligand 1，sPD-L1）、白介素-6（interleukin-6，IL-6）和白介素-10（interleukin-10，IL-10）的表达。每4周行MRI增强扫描，测量肿瘤体积。
      结果  客观缓解率（objective response rate，ORR）为33.33%（17/51），疾病控制率（disease control rate，DCR）为72.5%（37/51），中位无进展生存期（median progression-free survival，mPFS）为5.9个月，2年总生存期（overall survival，OS）为24.9%。最常见的不良反应为Ⅰ~Ⅱ级高血压和乏力。肿瘤体积的变化与用药后血清中sPD-1、sPD-L1和IL-6的变化显著相关（r=−0.846，P=0.001；r=0.874，P<0.001；r=0.769，P=0.003）；与IL-10的变化弱相关（r=0.538，P=0.071）。
      结论  阿帕替尼治疗TMZ耐药的GBM安全有效，且治疗中免疫因子发生变化并与疗效密切相关。

     

    Abstract:
      Objective  To investigate the efficacy and adverse effects of apatinib, a vascular endothelial growth factor receptor‐2inhibitor, in the treatment of temozolomide-resistant recurrent glioblastoma (GBM) and observe the changes in the expression of immune factors during treatment.
      Methods  Enrolled in Affiliated Cancer Hospital of Zhengzhou University from July 2018 to October 2020, 51 patients with recurrent GBM who did not respond satisfactorily to first-line treatment were treated with apatinib combined with temozolomide.They received 500 mg/day of apatinib for 2 weeks (d1-14), rested for 1 week, and started oral temozolomide (150 mg/m2/day for 5 consecutive days with a cycle of 28 days). Peripheral blood samples were collected before and after treatment, and the levels of soluble programmed cell death-1(sPD-1), soluble programmed death-ligand 1 (sPD-L1), interleukin (IL)-6, and IL-10 in the peripheral blood were detected using enzyme-linked immunosorbent assay (ELISA). Magnetic resonance imaging (MRI) was performed every 4 weeks to assess tumor volume.
      Results  The objective effective rate (ORR) was 33.33% (17/51). The disease control rate (DCR) was 75% (37/51). The median progression-free survival (mPFS) time was 5.9 months, and the 2-year overall survival (OS) rate was 24.9%. The most common adverse events were grade1-2 hypertension and fatigue. There was a significant correlation between changes in the levels of sPD-1(r=-0.846, P=0.001), sPD-L1 (r=0.874, P<0.001), and IL-6 (r=0.769, P=0.003) and a change in tumor volume. A weak and insignificant correlation (r=0.538, P=0.071) was found between a change in the IL-10 level and a change in tumor volume.
      Conclusions  Apatinib was safe and effective for the durg-resistant recurrent GBM, and changes in the expression of immune factors were closely related to the curative effect.

     

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