PMID- 33989780 OWN - NLM STAT- MEDLINE DCOM- 20210809 LR - 20230724 IS - 1556-1380 (Electronic) IS - 1556-0864 (Linking) VI - 16 IP - 8 DP - 2021 Aug TI - Efficacy and Safety of Intrathecal Pemetrexed Combined With Dexamethasone for Treating Tyrosine Kinase Inhibitor-Failed Leptomeningeal Metastases From EGFR-Mutant NSCLC-a Prospective, Open-Label, Single-Arm Phase 1/2 Clinical Trial (Unique Identifier: ChiCTR1800016615). PG - 1359-1368 LID - S1556-0864(21)02157-2 [pii] LID - 10.1016/j.jtho.2021.04.018 [doi] AB - INTRODUCTION: We aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating EGFR-mutant leptomeningeal metastases (LMs) from EGFR-mutant NSCLC. METHODS: Patients with EGFR-mutant NSCLC with LM who had failed tyrosine kinase inhibitors were recruited. The dose of IP was escalated from 15 mg to 80 mg using an accelerated titration design in a phase 1 study. The recommended dose (RD) determined in phase 1 was used in the phase 2 study. The primary end point was treatment efficacy measured as the clinical response rate. Overall survival and adverse events (AEs) were evaluated as secondary end points. RESULTS: 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. CONCLUSIONS: 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. CI - Copyright (c) 2021. Published by Elsevier Inc. FAU - Fan, Chengjuan AU - Fan C AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Zhao, Qiuyu AU - Zhao Q AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Li, Li AU - Li L AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Shen, Weixi AU - Shen W AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Du, Yang AU - Du Y AD - Department of Oncology, The Second Tumor Hospital of Heilongjiang Province, Harbin, People's Republic of China. FAU - Teng, Chong AU - Teng C AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Gao, Feng AU - Gao F AD - Department of Oncology, The Second Tumor Hospital of Heilongjiang Province, Harbin, People's Republic of China. FAU - Song, Xiaowei AU - Song X AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Jiang, Qiuying AU - Jiang Q AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Huang, Dayong AU - Huang D AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Jin, Yinghua AU - Jin Y AD - Department of Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Lv, Yanju AU - Lv Y AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Wei, Lingxiao AU - Wei L AD - Department of Oncology, Yunnan Cancer Hospital, Kunming, People's Republic of China. FAU - Shi, Tengfei AU - Shi T AD - Department of Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Zhao, Xue AU - Zhao X AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Gao, Naisheng AU - Gao N AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Jiang, Zhengjun AU - Jiang Z AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. FAU - Xin, Tao AU - Xin T AD - Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. Electronic address: xintao1234@263.net. LA - eng SI - ChiCTR/ChiCTR1800016615 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210511 PL - United States TA - J Thorac Oncol JT - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer JID - 101274235 RN - 0 (Protein Kinase Inhibitors) RN - 04Q9AIZ7NO (Pemetrexed) RN - 7S5I7G3JQL (Dexamethasone) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM CIN - J Thorac Oncol. 2021 Aug;16(8):1244-1246. PMID: 34304852 CIN - J Thorac Oncol. 2021 Oct;16(10):e82-e84. PMID: 34561041 CIN - J Thorac Oncol. 2021 Oct;16(10):e85. PMID: 34561042 CIN - J Thorac Oncol. 2022 Mar;17(3):e31-e32. PMID: 35216736 CIN - J Thorac Oncol. 2022 Mar;17(3):e33-e34. PMID: 35216737 CIN - J Thorac Oncol. 2023 Aug;18(8):e81-e82. PMID: 37479332 MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects MH - Dexamethasone/therapeutic use MH - ErbB Receptors/genetics/therapeutic use MH - Female MH - Humans MH - *Lung Neoplasms/drug therapy/genetics MH - Male MH - Mutation MH - Pemetrexed/therapeutic use MH - Prospective Studies MH - Protein Kinase Inhibitors/adverse effects OTO - NOTNLM OT - Intrathecal chemotherapy OT - Leptomeningeal metastases OT - NSCLC OT - Pemetrexed EDAT- 2021/05/15 06:00 MHDA- 2021/08/10 06:00 CRDT- 2021/05/14 20:12 PHST- 2020/11/25 00:00 [received] PHST- 2021/04/29 00:00 [revised] PHST- 2021/04/30 00:00 [accepted] PHST- 2021/05/15 06:00 [pubmed] PHST- 2021/08/10 06:00 [medline] PHST- 2021/05/14 20:12 [entrez] AID - S1556-0864(21)02157-2 [pii] AID - 10.1016/j.jtho.2021.04.018 [doi] PST - ppublish SO - J Thorac Oncol. 2021 Aug;16(8):1359-1368. doi: 10.1016/j.jtho.2021.04.018. Epub 2021 May 11.