High-dose methotrexate for metastatic breast cancer to the central nervous system: A single-institution review of 46 patients.

Abstract

1079 Background: The prognosis for patients with metastatic breast cancer to the central nervous system (CNS) is poor. Methotrexate (MTX) is an active agent in the treatment of breast cancer and penetrates the CNS at high doses and rapid rate of infusion. Methods: We performed an IRB approved retrospective review of patients treated at Northwestern from 8/1/2003 to 12/31/2013. Demographic data collected included date of diagnosis, time to CNS metastases, Karnofsky Performance Status, HER-2 and hormone status, radiographic and/or cytologic response to MTX, progression-free survival (PFS) and overall survival (OS). Results: Forty-six patients met criteria for inclusion. All patients were women with a median age of 49 (range 28-80) and average KPS of 70 (range: 20-100). Median number of doses was 4 (range 1-22), dosed at 3.5 gm/m2. The median PFS and OS were 3.4 and 4.1 months (m). Patients with ER/PR- disease had median PFS/OS of 5.2m/8.7m (HER2-) and 1.2m/3.0m (HER2 +). Patients with ER/PR+ disease had median PFS/OS of 3.4m/4.1m (HER2 -) and 3.4m/3.8m (HER2 +). When response was evaluated based on KPS, PFS/OS rates are 6.8m/15.2m for patients with KPS≥70. Patients with KPS<70 had PFS/OS rates of 3.2m/4.0m. Six patients are alive after completing MTX treatment and continue systemic therapies. There were 34 patients with scans for treatment evaluation: 1 complete response, 3 partial responses, and 16 patients had stable disease. Most common toxicities were anemia, hypokalemia, mucositis, transient elevations in liver enzymes, and thrombocytopenia. Conclusions: High-dose intravenous methotrexate remains a treatment option for patients with CNS metastases of breast cancer. Patients with ER/PR negative disease trended toward better PFS and OS. Patients with KPS less than 70 may not warrant treatment given shorter survival.