These agents inhibit cell growth and proliferation.
Methotrexate (Folex PFS, Rheumatrex)
Mainstay of treatment. Because meningeal infiltration interferes with drug clearance, CSF concentrations can be unpredictable. Monitor and maintain concentration near 10-6 M, and coadminister with folinic acid and hydrocortisone if necessary.
Second-line agent used if MTX not tolerated or ineffective. Not effective for solid tumors but useful in leukemic and lymphomatous meningitis. Half-life longer in CSF than serum. Sustained-release form available in United States; extends half-life to >140 h.
Third-line agent that acts as an alkylating agent. Intrathecal administration is an off-label use in the United States. It is cleared from CSF within minutes and has survival curves similar to those of methotrexate (MTX) with less neurologic toxicity (most common being transient limb paresthesias). Unlike MTX, no antidote for resulting myelosuppression is available. Causes cross-linking of DNA strands, inhibition of RNA, DNA, and protein synthesis, and thus cell proliferation.
Off-label intrathecal (IT) administration of trastuzumab has been described in several case reports. Trastuzumab is a monoclonal antibody that inhibits growth of tumor of tumor cells that overexpress HER2. It is an effective systemic treatment of breast cancer, and as such, the potential use of IT administration for LC secondary to breast cancer has shown improved prognosis and decreased progression in several case reports.