83P - Cerebral toxicity of whole brain radiotherapy plus icotinib in rats

Date 15 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Basic Science
Surgery and/or Radiotherapy of Cancer
Presenter Lin Zhou
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors L. Zhou1, R. Li1, F. Tang1, J. Liu2, R. Tong1, J. Xue1, Y. Liu1, S. Wang1, R. Zhong1, Y. Lu1
  • 1Department Of Thoracic Cancer, West China Hospital, Huaxi, Sichuan University, 610041 - Chengdu/CN
  • 2Department Of Oncology, Chengdu No 1 People's Hospital, Chengdu/CN

Abstract

Background

Whole-brain radiation therapy (WBRT) and epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) are both treatment options for EGFR-mutated NSCLC patients with brain metastases. This study aimed to investigate the possible cerebral toxicities caused by the combined treatment in rats.

Methods

Thirty-six, 12 weeks old, male, SD rats were randomized into 6 groups (6 rats in each group named A to F). Rats in group A and B received high dose (101.25 mg/kg qd) or low dose (33.75 mg/kg qd) icotinib (one kind of EGFR-TKIs) plus WBRT, group C and D received high dose or low dose icotinib only, group E received WBRT only, and group F was the sham control group. Icotinib was administered intragastrically once daily from day 1 and WBRT (30 Gy/5f/5d) was carried out 2 weeks later. All rats received Morris water maze test, including place navigation test and spatial probe test, at baseline, 4th week, 8th week, and 12th week to investigate their learning and memory abilities. All rates were sacrificed after the last water maze test, and the number of positive cells of GFAP (astrocyte), CD11b (microglia), and CNPase (oligodendrocyte) were evaluated in immunohistochemical samples from Hippocampus.

Results

There were no difference in the target finding latency and journey distance in place navigation tests between different groups and time points, neither in the percentage of stay time and journey distance of the target quadrant to total in spatial probing tests. Compare to group F, significantly more GFAP+ astrocytes could be observed in treatment groups (Group A to F: 87.4±15.8 vs. 92.8±28 vs. 91.7±14.4 vs. 92±19.6 vs. 87.6±16.6 vs. 64.8±24.4, p 

Conclusions

In rats, even there was no deterioration in cognitive function detected by water maze tests, pathological changes in hippocampus could be detected within a relatively short period after the combined treatment or icotinib treatment alone.

Clinical trial identification

Legal entity responsible for the study

Department of Thoracic Cancer, West China Hospital

Funding

“The 11th 5-year plan” for Technology Platform Construction of Innovative Drug Research and Development of China (2012ZX09303012–002) National Natural Science Fund of China (81301935, 81172131, 81472196) Betta Pharmaceuticals Co., Ltd

Disclosure

All authors have declared no conflicts of interest.