Intrathecal chemotherapy combined with systemic therapy in patients with refractory leptomeningeal metastasis of non-small cell lung cancer: a retrospective study

Abstract

Background Leptomeningeal metastasis (LM) is the most devastating complication of non-small cell lung cancer (NSCLC), and its incidence is increasing. There is currently no standard treatment for LM, and the efficacy of traditional intravenous drug treatment is low, making refractory LM a difficult problem. In this study, we evaluated the efficacy and safety of intrathecal chemotherapy (IC)-based regimens in patients with refractory LM. Methods We retrospectively enrolled NSCLC patients with confirmed LM who received IC and systemic therapy at the Second Affiliated Hospital of Nanchang University from December 2017 to July 2022. We analysed overall survival (OS), intracranial progression-free survival (iPFS), clinical response, and safety in these patients. Results A total of 41 patients were enrolled. The median number of IC treatments was seven (range: 2–22). Seven patients received intrathecal methotrexate, and 34 patients received intrathecal pemetrexed. Clinical manifestations related to LM improved after IC and systemic therapy in 28 (68.3%) patients. The median iPFS in the whole cohort was 8 months (95% confidence interval [CI]: 6.4–9.7 months), and the median OS was 10.1 months (95% CI: 6.8–13.4 months). Multivariate analysis of the 41 patients with LM using a Cox proportional risk model showed that bevacizumab was an independent prognostic factor in patients treated with combination therapy (p = 0.002; hazard ratio [HR] 0.240; 95% CI: 0.097–0.595). Poor ECOG performance status remained a significant predictor of poor prognosis for survival (p = 0.048; HR 2.560; 95% CI: 1.010–6.484). Myelosuppression was the major adverse event over all IC dose levels. There were 18 cases of myelosuppression, 15 cases of leukopenia, and nine cases of thrombocytopenia. Eleven patients had myelosuppression above grade 3, including four with thrombocytopenia and seven with leukopenia. Conclusions Combination therapy based on IC had good curative effects, was safe to use, and was associated with prolonged survival in NSCLC patients with LM. The use of bevacizumab is a good prognostic factor for NSCLC LM patients with combination therapy.

Intrathecal pemetrexed in patients with EGFR-TKI resistant refractory leptomeningeal metastasis lung adenocarcinoma : a retrospective study

“…The drug is directly delivered to the subarachnoid space through lumbar puncture, which can make the drug evenly distributed along the subarachnoid space, directly act on the arachnoid and increase the drug concentration. Recently, more and more studies have shown that intrathecal injection has a good effect on tumor leptomeningeal metastasis, such as solid tumors such as breast cancer and lung cancer [11,15,[17][18][19]. All patients in this study were accompanied by obvious neurological symptoms, which seriously affected the quality of life of the patients.…”

“…The main relevant factors reported were KPS score (median OS 12 months vs 6months), and high ECOG score was an important predictor of poor survival prognosis. Univariate analysis suggested that previous history of whole brain radiotherapy was associated with better prognosis, and multivariate analysis suggested that the combination of bevacizumab was an independent prognostic factor for intrathecal injection therapy [11,15,20,26]. The LM OS of ID2 combined with whole brain radiotherapy was signi cantly better than the median LM OS, suggesting that whole brain radiotherapy may be a prognostic factor affecting leptomeningeal metastasis of lung cancer.…”

“…Recently, some studies have shown that pemetrexed can also be used in intrathecal chemotherapy. A prospective open-label single-arm phase 1/2 clinical study showed that the clinical response rate of intrathecal pemetrexed in EGFR-mutated non-small cell lung cancer was 84.6% (22/26), and the median overall survival was 9.0 months [11]. Another retrospective cohort study showed that in the mode of intrathecal chemotherapy (pemetrexed or methotrexate) combined with systemic therapy, the median intracranial progression-free survival (iPFS) of non-small cell lung cancer with leptomeningeal metastasis was eight months (95%CI 6.4-9.7 months), and the median OS was 10.1 months (95%CI: 6.8-13.4 months) [12].…”