Ctni-13. concurrent intrathecal chemotherapy and involved-field radiotherapy for leptomeningeal metastasis from solid tumors: a phase ii study (nct03082144)

Abstract BACKGROUND The role of involved-field radiation therapy (IFRT) and intrathecal chemotherapy (IC) in leptomeningeal metastasis (LM) from solid tumors was gradually underestimated in the era of targeted therapy. This study was aimed to investigate the safety and effectiveness of concurrent IFRT and intrathecal methotrexate (MTX)/cytarabine (Ara-C) for LM, particularly for those who developed LM while receiving targeted therapy. METHODS Enrolled patients were randomly assigned to two subgroups (IFRT&IC-MTX and IFRT&IC-Ara-C), and first treated with induction IC (MTX or Ara-C) twice per week, up to 4 times. Then patients were given concurrent treatment, which consisted of IFRT (40 Gy total; 2 Gy/f) and IC (MTX 15 mg or Ara-C 50 mg, once per week). The involved field consisted of symptomatic or painful sites and disease observed on magnetic resonance imaging (MRI), including the whole brain and basis crania and/or segment of spinal canal. Primary endpoint was clinical response rate (RR). Secondary endpoints were safety and overall survival (OS). RESULTS Fifty-three patients received induction intrathecal MTX (n = 27) or Ara-C (n = 26). Forty-two patients completed concurrent therapy. Total RR was 34% (18/53). The improvement rate of neurological symptoms and KPS scores were 72% (38/53) and 66% (35/53) respectively. Adverse events (AEs) rate was 28% (15/53). Eight patients (15%, 8/53) showed grade 3-4 AEs, including myelosuppression (n = 4) and radiculitis (n = 5). Median OS was 6.5 months (95% CI, 5.3-7.7 months). Median survival for 18 patients who had clinical response was 7.9 months (95% CI, 4.4-11.4 months), and 0.8 months (95% CI, 0.08-1.5 months) for 6 patients who had LM progression. The median survival in 22 patients who received prior targeted therapy was 6.3 months (95% CI, 4.5-8.1 months). CONCLUSION Concurrent IFRT and intrathecal MTX or Ara-C was proved to be a feasible treatment option with an acceptable safety profile for LM from a common tumor entity.