Umekawa Kanako, Kimura Tatsuo, Kudoh Shinzoh, Suzumura Tomohiro, Nagata Misato, Mitsuoka Shigeki, Matsuura Kuniomi, Oka Takako, Yoshimura Naruo, Kira Yukimi, Hirata Kazuto
Department of Respiratory Medicine, Osaka City University, Graduate School of Medicine, Japan.
Osaka City Med J. 2013 Jun;59(1):53-60.
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are routinely used to treat advanced non-small cell lung cancer (NSCLC) patients with activated EGFR mutations, and are associated with excellent response and improvement of performance status. Adipose tissue produces and releases substances called adipokines, which include adiponectin, leptin, resistin, and hepatocyte growth factor (HGF), etc. Previously, we reported that high levels of plasma HGF at diagnosis indicated intrinsic resistance to EGFR-TKIs. EGFR-TKIs have been hypothesized to affect these adipokines.
This prospective study, to evaluate the correlation between plasma adiponectin and insulin levels and non-hematological adverse effects in advanced NSCLC following EGFR-TKIs administration, was conducted at the Osaka City University Hospital. Plasma adiponectin and insulin levels were determined at diagnosis and on treatment day 30.
Overall 33 patients were enrolled. We obtained plasma samples for analyses from all patients at diagnosis and from 26 patients on day 30. Increased adiponectin (13.69 to 14.42 microg/mL, p = 0.0092), and decreased insulin (404.0 to 351.2 pg/mL, p = 0.022) were observed after EGFR-TKI treatments. High levels of adiponectin at diagnosis were associated with severities of skin rash (p = 0.035).
The adiponectin was affected by EGFR-TKI treatments for NSCLC. Besides, the adverse events by EGFR-TKIs were influenced by the plasma adipokines at diagnosis. Our study may provide useful information regarding patient outcomes to EGFR-TKI treatments. A prospective large clinical trial is warranted to clarify these results.
表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）通常用于治疗具有激活型EGFR突变的晚期非小细胞肺癌（NSCLC）患者，且与良好的反应及体能状态改善相关。脂肪组织产生并释放称为脂肪因子的物质，其中包括脂联素、瘦素、抵抗素和肝细胞生长因子（HGF）等。此前，我们报道过诊断时血浆HGF水平高表明对EGFR-TKIs存在内在抗性。据推测，EGFR-TKIs会影响这些脂肪因子。
这项前瞻性研究在大阪市立大学医院开展，旨在评估EGFR-TKIs给药后晚期NSCLC患者血浆脂联素和胰岛素水平与非血液学不良反应之间的相关性。在诊断时及治疗第30天测定血浆脂联素和胰岛素水平。
共纳入33例患者。我们在诊断时获取了所有患者的血浆样本用于分析，并在第30天获取了26例患者的样本。EGFR-TKI治疗后观察到脂联素增加（从13.69至14.42微克/毫升，p = 0.0092），胰岛素降低（从404.0至351.2皮克/毫升，p = 0.022）。诊断时脂联素水平高与皮疹严重程度相关（p = 0.035）。
脂联素受NSCLC的EGFR-TKI治疗影响。此外，EGFR-TKIs的不良事件受诊断时血浆脂肪因子影响。我们的研究可能为EGFR-TKI治疗的患者预后提供有用信息。有必要进行一项前瞻性大型临床试验来阐明这些结果。
