Abstract

BackgroundInfusion of high-dose intravenous methotrexate (MTX) has been demonstrating to penetrate the blood-brain barrier. The aim of this present study was to assess the efficacy and safety of high dose MTX in patients with central nervous system (CNS) metastases of breast cancer.MethodsTwenty-two patients with CNS metastases treated by MTX (3 g/m2) between April 2004 and October 2009 were enrolled. Clinical response rate, time to progression (TTP), overall survival (OS), and safety were assessed.ResultsIn terms of brain metastases, 2 patients (9%) achieved a partial response, 10 patients (45%) had disease stabilization, and 10 patients (45%) had disease progression. In others metastatic sites, 7 patients (39%) achieved a disease stabilization, and 11 patients (61%) had disease progression. TTP and OS were 2.1 (95%CI 1.4–2.9) and 6.3 (95%CI 1.8–10) months, respectively.ConclusionHigh-dose MTX demonstrated a moderate activity at 3 g/m2. Nonetheless, the favorable toxicity profile should suggest the possibility to increase the dosage and further study are planned.

Highlights

  • Infusion of high-dose intravenous methotrexate (MTX) has been demonstrating to penetrate the blood-brain barrier

  • Central nervous system (CNS) metastases is a dismal evolution which results in devastating disease with progressive neurologic disability and death

  • Despite the progress made in treatment of extraneural metastatic breast cancer, therapeutic options for central nervous system (CNS) metastases are limited and they provide a median survival shorter than 1 year [6]

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Summary

Introduction

Infusion of high-dose intravenous methotrexate (MTX) has been demonstrating to penetrate the blood-brain barrier. The aim of this present study was to assess the efficacy and safety of high dose MTX in patients with central nervous system (CNS) metastases of breast cancer. Patients with metastatic breast cancer (MBC) are at high risk for CNS metastases with a rate of occurrence ranged between 10 to 42% [1,2,3,4,5]. Despite the progress made in treatment of extraneural metastatic breast cancer, therapeutic options for CNS metastases are limited and they provide a median survival shorter than 1 year [6]. Systemic treatments provide a low rate of efficacy because most of chemotherapeutic agents are excluded from the CNS by the Blood-Brain Barrier (BBB) [8]

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