Acute-phase reaction induced by zoledronate and its effect on prognosis of patients with advanced non-small cell lung cancer

作者：Izumi Hiroki^*; Yamasaki Akira; Takeda Kenichi; Kodani Masahiro; Touge Hirokazu; Tanaka Natsumi; Yanai Masaaki; Ueda Yasuto; Sakamoto Tomohiro; Nishii Ito Shizuka; Makino Haruhiko; Yamaguchi Kosuke; Igishi Tadashi; Shimizu Eiji

来源：Lung Cancer, 2018, 122: 200-205.

DOI：10.1016/j.lungcan.2018.06.022

• Non-small cell lung cancer
• Zoledronate
• Acute-phase reaction
• gamma delta T cell
• Epidermal growth factor receptor

Objectives: Zoledronate (ZOL) is usually used for prevention of skeletal-related events in cancer patients with bone metastases. The first administration of ZOL is occasionally associated with development of acute-phase reaction (APR), which is due to activation of gamma delta T cells. ZOL-related APR was associated with better overall survival (OS) of patients with non-small cell lung cancer (NSCLC) in our previous retrospective study. However, it remains to be clarified whether gamma delta T cells are more activated in patients who experienced ZOL-related APR, and whether gamma delta T cell activation is involved in prolongation of OS.
Materials and Methods: Twenty-three patients with advanced NSCLC were recruited between 2012 and 2014 in this study. We administered ZOL to participants with standard care. The patient characteristics, change in gamma delta T cell counts and cytokines, OS, and skeletal-related event-free survival were compared between patients with APR (APR group) and those without APR (non-APR group).
Results: Ten patients (43.5%) experienced a ZOL-related APR. The number of gamma delta T cells at baseline in the APR group was significantly higher than that in the non-APR group. Serum interleukin-6 and tumor necrosis factor-a in the APR group were significantly increased, but no change in the number of gamma delta T cells was observed after the first administration of ZOL in both groups. OS in the APR group was significantly longer than that in the non-APR group (median survival time: 23.1 vs. 14.5 months, p < 0.01).
Conclusion We showed that APR is related to higher numbers of gamma delta T cells at baseline and increased cytokines after the first ZOL administration, but not to proliferative responses of gamma delta T cells. In addition, better OS was observed in the APR group. Therefore, the number of gamma delta T cells might be a prognostic marker in patients with NSCLC.

• 出版日期2018-8