High-dose intravenous methotrexate in the management of breast cancer with leptomeningeal disease: Case series and review of the literature

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

“…The limited success of chemotherapy against brain tumours is caused mainly by low CNS drug penetration through the BBB [242]. MTX brain penetration is poor and due to its application at LDMTX is insufficient to achieve therapeutic concentration in the brain [190,191,[243][244][245]. In order to attain the desirable MTX concentration in brain cancer, administration of HDMTX is required and current efforts in the field of MTX brain tumour therapy focuses mainly on the design of novel, non-invasive, safe and effective MTX delivery systems for cerebral treatment [199,[246][247][248].…”

“…MTX is used (alone or in combination) to treat both early-stage (as well after surgery and other treatments) and advanced-stage breast cancer. Some selected application of MTX in breast cancer therapy are presented below [196,[213][214][215][216][217][218][219][220][221]244,[265][266][267], Table 2. Martin et al described numerous combination regimens applied in metastatic breast cancer, such as CTX, MTX, 5-FU (CMF), 5-FU, Adriamycin, CTX (FAC) and MTX in combination with tegafur and uracil followed by LV rescue (MUL) [213,214].…”

“…Breast cancer usually spreads to the CNS inducing commonly leptomeningeal metastasis. Kapke et al determined that systemic intravenously administration of HDMTX, improves quality of life and provides durable remissions for leptomeningeal metastasis of breast cancer [244]. Application of MTX in a form of iron oxide NPs for human breast cancer therapy is given in the paper of Kohler et al [196].…”

Prognostic factors and therapeutic perspectives of meningeal carcinomatosis in patients with breast cancer: A case report and review of the literature

“…In most cases the goal is to stabilize and/or improve the quality of life and extend survival [3]. A standard treatment scheme has not yet been formulated, but among the existing options are radiotherapy, intrathecal chemotherapy and systemic chemotherapy [4], which can be used according to individual needs. Although the prognosis varies according to type, degree of neoplasm and characteristics of the individual, some parameters can help differentiate high-risk patients (low performance status, presence of neurological deficits, advanced disease) from low-risk ones (good health, little or no neurological deficit, limited disease).…”

“…As treatment has not yet been standardized, it would be advisable to individualize it in each patient with regard to their underlying pathology, comorbidities and ability to respond to therapy [2]. In particular, the options in breast cancer include radiotherapy, intrathecal and systemic chemotherapy [4]. Prognosis is generally poor with a mean total survival of about 3-4 months from diagnosis, with better results in hematological and treatment-sensitive solid cancers [1].…”