Safety, Pharmacokinetic and Clinical Activity of Intrathecal Chemotherapy With Pemetrexed via the Ommaya Reservoir for Leptomeningeal Metastases From Lung Adenocarcinoma: A Prospective Phase I Study

作者：Huiying Li, Shengnan Zheng, Yongjuan Lin, Tingting Yu, Yu Xie, Cheng Jiang, Xiangyu Liu, Xiaoping Qian, Zhenyu Yin · 发表于：Clinical Lung Cancer · 年份：2022 · DOI：10.1016/j.cllc.2022.11.011 · 被引用次数：34 · 研究领域：Brain Metastases and Treatment、Lung Cancer Diagnosis and Treatment、Management of metastatic bone disease

INTRODUCTION: Leptomeningeal metastasis (LM) is a highly fatal and debilitating complication of lung adenocarcinoma (LUAD) with limited therapeutic options. This study aimed to evaluate the efficacy and toxicities of intrathecal chemotherapy (IC) with pemetrexed via Ommaya reservoir in LUAD with refractory LM. METHODS: In this prospective, single-arm, phase I trial (ChiCTR2000028936), LUAD-LM patients who had progressed after at least two prior treatments were recruited. Pemetrexed from 30 mg to 50 mg was administered on Days 1 and 8 every 3 weeks via Ommaya reservoir. Serial samples of cerebrospinal fluid (CSF) and plasma were obtained for pharmacokinetic studies. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and therapeutic toxicities. RESULTS: Twenty-three patients were enrolled and analyzed, revealing an ORR of 43.5% (95% CI, 23.2%-63.8%) and DCR of 82.6% (95% CI, 61.2%-95.0%). The median PFS and OS were 6.3 and 9.5 months, respectively. Dose-limiting toxicity was only observed in 2 patients (2/23, 8.7%), and 30 mg pemetrexed was considered as the recommended dose for IC. Pharmacokinetic analysis showed that using Ommaya reservoirs, higher pemetrexed concentrations and prolonged half-lives were achieved in the CSF compared with lumbar puncture (LP). CONCLUSIONS: Intrathecal pemetrexed at a dose of 30 mg via Ommaya reservoirs on Days 1 and 8 ev...