Abstract
Objective This retrospective study aimed to investigate the clinical features of lung cancer patients with leptomeningeal metastasis (LM) and explore the clinical efficacy and tolerance of intrathecal pemetrexed (IP) combined with systemic antitumor therapy. Methods Thirty-four lung cancer patients (11 men, 23 women) with LM receiving IP at our hospital were retrospectively reviewed between August 2018 and December 2019. Identified cases showed either positive cerebrospinal fluid cytology or typical findings (leptomeningeal enhancement or ventricle broadening) upon imaging examination. Results Before the diagnosis of LM, 24 (70.6%) patients received EGFR-TKI therapy with or without other agents (antivascular therapy, or chemotherapy), 5 (14.7%) patients received chemotherapy, 1 (2.9%) patient received antivascular therapy, and 3 (8.8%) patients received ALK inhibitors. Fourteen (41.2%) patients did not change the systematic regimen at the beginning of IP, while 20 (58.8%) patients changed to antitumor agents. IP was administered for a median of 3 times (range, 1-12 times). The IP dose was 15, 20, 25, 30, and 40 mg in 8 (23.5%), 21 (58.8%), 2 (5.9%), 2 (5.9%), and 1 (5.9%) patient, respectively. In all IP dose levels, the major adverse events were myelosuppression and elevation of hepatic aminotransferases (EHA). Grade 1/2 myelosuppression occurred in 4 (11.8%) patients. Grade 1/2 EHA also occurred in 4 (11.8%) patients. Grades 3/4 adverse events were not observed. After IP and systematic therapy, the clinical manifestations related to LM in 26 (76.5%) patients improved. In the whole cohort, the median overall survival was 20 months. The median time from the initial IP administration until death or the last follow-up was 3.5 months. Conclusions IP showed controllable toxicity and good efficacy, prolonged the survival time, and improved the quality of life when combined with tailored systemic antitumor therapy in lung cancer patients.