Clinical efficacy and safety of different doses of intrathecal methotrexate in the treatment of leptomeningeal carcinomatosis: a prospective and single-arm study.

Objective: To investigate the clinical efficacy and safety of different doses of intrathecal methotrexate in the treatment of leptomeningeal carcinomatosis.

Methods: 53 patients admitted to the Second Hospital of Hebei Medical University with leptomeningeal carcinomatosis were recruited. They were divided into two groups: 15-mg-group received 15 mg methotrexate intrathecally, while the other received 10 mg methotrexate. All patients were followed up to 31 December 2020 or until death. Primary endpoint was the response rate. Secondary endpoints were survival and safety. Treatment-related adverse events were recorded.

Results: The intrathecal chemotherapy was regularly maintained in 42 cases. Most primary cancers were lung (60.4%), stomach (18.9%) or breast (5.7%). The clinical response rate was higher in the 15 mg group than the 10 mg group (62.5 vs. 34.5%, P = 0.042). In the 15 mg group, two cases showed myelosuppression and one case showed seizures. In the 10 mg group, one patient appeared fever, three patients appeared myelosuppression and one showed leukoencephalopathy. However, there were no serious irreversible adverse reactions in neither of the two groups. In terms of survival, the median survival was 15.7 weeks in the 15 mg group and 27.1 weeks in the 10 mg group (P = 0.116). Multivariate analysis showed that only targeted therapy improved the survival (P < 0.0001, HR = 5.386).

Conclusion: Increased dose of methotrexate did not prolong the overall survival, but it was more effective in relieving clinical symptoms with no increased adverse reactions. Targeted therapy might improve the survival.