[Huangqi Guizhi Wuwu Decoction in the Treatment of Pemetrexed Intrathecal Chemotherapy-induced Neurotoxicity in NSCLC Patients with Leptomeningeal Metastases: A Randomized Controlled Trial].

Abstract

Background: Leptomeningeal metastasis (LM) is a severe complication of non-small cell lung cancer (NSCLC). Although intrathecal Pemetrexed chemotherapy can effectively prolong patient survival, a high incidence of neurotoxicity has emerged as a critical factor limiting its clinical application. This study aims to investigate the efficacy and safety of Huangqi Guizhi Wuwu decoction (HGWD) in mitigating neurotoxicity induced by intrathecal Pemetrexed chemotherapy in NSCLC patients with LM.

Methods: In a prospective, randomized, double-blind, controlled trial, 220 NSCLC patients with LM were enrolled and randomly assigned to either the treatment group (HGWD+intrathecal chemotherapy) or the control group (placebo+intrathecal chemotherapy), with 110 patients in each group. The incidence and grade of neurotoxicity, disease control rate (DCR), progression-free survival (PFS), overall survival (OS), quality of life, and adverse reactions were observed and compared between the two groups.

Results: The incidence of neurotoxicity in the treatment group was 29.1%, significantly lower than that in the control group (51.8%)(P<0.001). The incidences of both grade 1-2 and grade 3-4 neurotoxicity were lower in the treatment group than in the control group (P<0.010). Nerve conduction studies showed that the sensory nerve action potential amplitude of the sural nerve was significantly higher in the treatment group than in the control group (P=0.012), and the conduction velocities of the median and ulnar nerves showed a trend toward improvement. The DCR was 76.4% in the treatment group, higher than 69.1% in the control group (P=0.045). Both median PFS (7.8 vs 6.1 mon, P<0.001) and median OS (10.5 vs 8.9 mon, P=0.007) were significantly prolonged in the treatment group. Improvements in quality of life and traditional Chinese medicine syndrome scores were superior in the treatment group (P<0.05). No significant difference in adverse reactions were observed.

Conclusions: HGWD can significantly reduce the incidence of neurotoxicity induced by Pemetrexed intrathecal chemotherapy, improve chemotherapy tolerance and survival benefits, with a good safety profile in NSCLC patients with LM.