We aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating EGFR-mutant leptomeningeal metastases (LMs) from EGFR-mutant NSCLC. The RD observed in the phase 1 study was 50 mg pemetrexed. A total of 30 cases of LM-NSCLC were enrolled in the phase 2 study, including 14 males and 16 females. Four patients did not survive for 4 weeks and could not be evaluated for efficacy. The clinical response rate was 84.6% (22 of 26). The median overall survival of all patients was 9.0 months (n = 30, 95% confidence interval: 6.6–11.4 mo). Most AEs were mild, and the most frequent AE of any grade was myelosuppression (n = 9, 30%), which returned to normal after symptomatic treatment. This study revealed that 50 mg pemetrexed is the RD which results in few AEs and a good response rate. IP is an effective treatment for patients with EGFR-mutant NSCLC-LM who had failed on tyrosine kinase inhibitor...... READ ARTICLE
Journal of Thoracic Oncology DOI:10.1016/J.JTHO.2021.04.018
Authors: Chengjuan Fan, Qiuyu Zhao, Li Li, Weixi Shen, Yang Du, Chong Teng, Feng Gao, Xiaowei Song, Qiuying Jiang, Dayong Huang, Yinghua Jin, Yanju Lv, Lingxiao Wei, Tengfei Shi, Xue Zhao, Naisheng Gao, Zhengjun Jiang, Tao Xin
Background: The aim of this study is to elucidate the mechanisms of acquired resistance to pemetrexed in echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer. Methods: We analyzed the sensitivity to pemetrexed and the expression patterns of various proteins after pemetrexed treatment in the cell lines, A549, NCI-H460, NCI-H2228 harboring EML4-ALK variant 3, and NCI-H3122 harboring EML4-ALK variant 1. Pemetrexed-resistant cell lines were also generated through long-term exposure to pemetrexed. Results: The EML4-ALK variant 1 rearranged NCI-H3122 was found to be more sensitive than the other cell lines. Cell cycle analysis after pemetrexed treatment showed that the fraction of cells in the S phase increased in A549, NCI-H460, and NCI-H2228, whereas the fraction in the apoptotic sub-G1 phase increased in NCI-H3122. The pemetrexed-resistant NCI-H3122 cell line showed increased expression of EGFR and HER2 compared to ..... READ ARTICLE
Cells DOI:10.3390/cells8121538
Authors: Ji-Hyun Kwon, Kui-Jin Kim, Ji Hea Sung, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Jin Won Kim, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Soyeon Kim, Sung-Soo Yoon, Jong Seok Lee