Prospective Evaluation Of High-Dose Systemic Methotrexate In Patients With Breast Cancer And Leptomeningeal Metastasis

Summary

Participation Requirements

Description

BACKGROUND: Management of LMD in patients with metastatic breast cancer is an area of unmet clinical need. Increased survival in the era of hormonal and HER2 directed therapies has further heightened the need for more effective therapies against the late complications of metastatic disease. Prognosi...

BACKGROUND: Management of LMD in patients with metastatic breast cancer is an area of unmet clinical need. Increased survival in the era of hormonal and HER2 directed therapies has further heightened the need for more effective therapies against the late complications of metastatic disease. Prognosis is dismal with median survivals ranging from 6-8 weeks in untreated patients and with little improvement having been demonstrated over the past 20 years. Recently, there has been renewed interest in systemic chemotherapeutic options in these patients. Incorporation of systemic therapies into standard treatment algorithms has been limited as many agents have not been shown to adequately penetrate the blood brain barrier. High-dose methotrexate (HD-MTX), however, is unique in that it does penetrate the blood brain barrier. In fact, evidence suggests that it may target areas of poor cerebrospinal fluid (CSF) flow, penetrate bulk disease, and provide treatment to systemic disease burden. Methotrexate is a drug known to have activity against breast cancer and has been used in combination with cyclophosphamide and 5-fluorouracil as part of a standard adjuvant treatment regimen. Currently, HD-MTX is included in the NCCN Guidelines for LMD and is used intermittently at Johns Hopkins and cancer centers across the nation for LMD in breast cancer. These recommendations, however, are more representative of the lack of available therapies for LMD as opposed to strong evidence-based data. Only two retrospective studies have suggested that HD-MTX may be an effective option for treating central nervous system (CNS) metastasis, both with substantial methodological limitations. STUDY OBJECTIVE This phase II, prospective study will evaluate systemic, intravenous high-dose methotrexate (HD-MTX) in breast cancer patients with leptomeningeal metastasis (LMD). The primary objective is to determine if treatment with systemic intravenous HD-MTX will result in an overall survival (OS) exceeding 12 weeks among patients with triple negative, HER2-positive, and hormone refractory metastatic breast cancer patients with LMD with and without parenchymal brain involvement.

Tracking Information