A retrospective case series of 103 consecutive patients with leptomeningeal metastasis and breast cancer

Abstract

Approximately 2-5 % of patients with breast cancer (BC) develop leptomeningeal metastasis (LM). 103 consecutive patients with BC were diagnosed with LM and initially treated with intra-CSF liposomal cytarabine from 2007 to 2011 at a single institution. Correlations were determined with respect to patient characteristics and BC subtype with regard to overall survival (OS). At LM diagnosis, 61 % of patients had a 0-2 performance status (PS), the remaining 39 % were severely neurologically impaired. Regardless of PS, all patients received intra-cerebrospinal fluid (CSF) liposomal cytarabine as first-line treatment. Systemic treatment and radiotherapy were also given in 58 and 17 % of patients respectively as clinically appropriate. Second- (intra-CSF thiotepa) and third-line (intra-CSF methotrexate) treatment was administered in 24 and 6 patients respectively. Median OS was 3.8 months (range 1 day-2.8 years). In multivariate analysis, an initial combined treatment, a second-line treatment with intra-CSF thiotepa, an initial clinical response, and a non-'ER/PR/HER2 negative' BC were significantly associated with a better OS. Median OS in this heterogeneous retrospective case series was similar to that of previously observed BC patients treated with intra-CSF methotrexate suggesting intra-CSF liposomal cytarabine is a reasonable first choice therapy of BC-related LM.

Efficacy of Liposomal Cytarabine in the Treatment of Leptomeningeal Metastasis of Breast Cancer

“…systemic treatment, intrathecal drug administration and radiotherapy, might have a positive influence on the outcome of the patient. A positive influence of an initially combined treatment was confirmed in the investigation of Le Rhun et al [11] and is supported by the literature review of Scott et al [12]. Some of the current known negative predicting factors could not be confirmed in this case.…”

“…The response rates of 26-72% and median time to neurological progression of 58-105.5 days were observed in these cohorts [8][9][10]. The efficacy of the liposomal cytarabine in breast cancer patients with LM has been analyzed in a smaller number of trials: the median time to neurological progression of 49 days and 2.1 months was shown by Jaeckle et al [7] and Le Rhun et al [11].…”

Safety and Efficacy of Liposomal Cytarabine in the Treatment of Neoplastic Meningitis

“…However, the median survival was reported to be only 99.5 days for liposomal cytarabine in the Glantz study group, which compares to a rather long median OS of 11 months in our study cohort. Of note, in contrast to other studies, almost all of our patients received concomitant systematic chemotherapy and/or irradiation, which might be one explanation for the prolonged survival [16]. Furthermore, we also included patients with primary CNS tumors who have received liposomal cytarabine since the beginning of the initial diagnosis and showed a favorable survival in comparison to other tumor types.…”

Breast Cancer Leptomeningeal Metastasis: The Results of Combined Treatment and the Comparison of Methotrexate and Liposomal Cytarabine As Intra–Cerebrospinal Fluid Chemotherapy

“…3,4 In contrast to radiotherapy, the role of systemic intravenous/oral therapy in prolongation of survival of patients with LM has been established. [3][4][5][6][7] The role of intra-CSF chemotherapy remains to be defined. The benefit of intra-CSF chemotherapy in patients with breast cancer and LM has never been demonstrated in randomized clinical trials.…”

“…Four intra-CSF agents (methotrexate, free cytarabine, liposomal cytarabine, and thiotepa) are used in patients with breast cancer. 1,2,6,8 Intrathecal methotrexate has been used for a long time in patients with breast cancer LM. Liposomal cytarabine had been tested in a few studies including patients with breast cancer LM.…”