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Old 11-02-2015, 10:01 PM   #31
Jackie07
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Re: Compiling Data on HER2 Brain Mets

Found three abstracts of recent research articles on the subject (Leptomeningeal metastasis (LM) in breast cancer patients) via PubMed database http://www.ncbi.nlm.nih.gov/pubmed:

Neurol Sci. 2015 Sep;36(9):1691-3. doi: 10.1007/s10072-015-2259-1. Epub 2015 May 20.
Intravenous thiotepa for treatment of breast cancer-related leptomeningeal carcinomatosis: case series.
Chahal J1, Stopeck A, Clarke K, Livingston RB, Chalasani P.
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Abstract
Leptomeningeal carcinomatosis (LMC) secondary to metastatic breast cancer (MBC) has increased in incidence with improved systemic disease control. Current treatment options include radiation therapy (to symptomatic sites) and systemic treatment [intrathecal (IT) or intravenous (IV) chemotherapy]. Methotrexate (MTX), thiotepa and cytarabine are the most commonly used IT agents, while high-dose MTX is the most common IV regimen. While IT treatments are generally well tolerated, complications like chemical meningitis, leukoencephalopathy, etc. occur. LMC may cause a breakdown in the blood-brain barrier and thus allow systemic agents to penetrate; however, efficacy is reported only for agents administered at high doses (MTX). We report our institution's experience in using IV thiotepa as treatment for LMC secondary to MBC. We conducted a retrospective chart review of 13 patients with MBC who developed LMC and treated with IV thiotepa at our institution. It was administered at 40 mg/m(2) every 21 days; median number of thiotepa cycles administered was 5 with the major dose-limiting toxicity being myelosuppression. Four had partial response, 3 had stable disease and 6 had progressive disease. The 6-month survival rate was 69 % and 1-year survival rate was 31 %. Despite retrospective nature of our case series, we found the use of IV thiotepa as sole treatment for LMC in patients with MBC to be well tolerated, easily administered in the ambulatory setting, and with efficacy comparable to the other chemotherapeutic agents commonly used in the treatment of LMC. This regimen warrants further investigation in prospective studies.

BMC Cancer. 2015 Apr 17;15:299. doi: 10.1186/s12885-015-1290-1.
A pilot study of bevacizumab combined with etoposide and cisplatin in breast cancer patients withleptomeningeal carcinomatosis.
Wu PF1, Lin CH2, Kuo CH3, Chen WW4, Yeh DC5, Liao HW6, Huang SM7, Cheng AL8,9,10, Lu YS11,12.
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Abstract
BACKGROUND:
Elevated vascular endothelial growth factor (VEGF) was associated with poor prognosis in leptomeningeal carcinomatosis and anti-angiogenic therapy was found to prolong the survival of mice in preclinical studies. This prospective pilot study investigated the efficacy of anti-VEGF therapy plus chemotherapy in patients with leptomeningeal carcinomatosis originating from breast cancer.
METHODS:
Eligible patients were scheduled to receive bevacizumab combined with etoposide and cisplatin (BEEP) every 3 weeks for a maximum of 6 cycles or until unacceptable toxicity. The primary objective was the central nervous system (CNS)-specific response rate, which was defined as disappearance of cancer cells in the cerebrospinal fluid (CSF) and an improved or stabilized neurologic status. The impact of VEGF inhibition on etoposide penetration into the CSF was analyzed.
RESULTS:
Eight patients were enrolled. The CNS-specific response rate was 60% in 5 evaluable patients. According to intent-to-treat analysis, the median overall survival of the eight patients was 4.7 months (95% confidence interval, CI, 0.3-9.0) and the neurologic progression-free survival was 4.7 months (95% CI 0-10.5). The most common grade 3/4 adverse events were neutropenia (23.1%), leukopenia (23.1%), and hyponatremia (23.1%). The etoposide concentrations in the CSF were much lower than those in plasma, and bevacizumab did not increase etoposide delivery to the CSF.
CONCLUSIONS:
BEEP exhibited promising efficacy in breast cancer patients with leptomeningeal carcinomatosis. Additional studies are warranted to verify its efficacy and clarify the role of anti-angiogenic therapy in this disease.

J Clin Neurosci. 2015 Apr;22(4):632-7. doi: 10.1016/j.jocn.2014.10.022. Epub 2015 Feb 9.
Treatment of leptomeningeal carcinomatosis: current challenges and future opportunities.
Kak M1, Nanda R2, Ramsdale EE3, Lukas RV4.
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Abstract
Leptomeningeal metastasis (LM) in breast cancer patients confers a uniformly poor prognosis and decreased quality of life. Treatment options are limited and often ineffective, due in large part to limitations imposed by the blood-brain barrier and the very aggressive nature of this disease. The majority of studies investigating the treatment of LM are not specific to site of origin. Conducting randomized, disease-specific clinical trials in LM is challenging, and much clinical outcomes data are based on case reports or retrospective case series. Multiple studies have suggested that chemo-radiotherapy is superior to either chemotherapy or radiation therapy alone. Attempts to overcome current obstacles in the treatment of breast cancer LM hold promise for the future. We review the epidemiology, diagnosis, and prognosis of LM in breast cancer, and discuss the treatment options currently available as well as those under investigation.

PS. Lani posts regularly new findings/researches about Her2 breast cancer. We can use the 'Search' button on the top bar to locate new articles by typing in 'Lani' and/or specific subject (eg. Lani and 'brain mets'). Sort of a short cut. http://her2support.org/vbulletin/sea...archid=1884595
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Last edited by Jackie07; 11-02-2015 at 10:23 PM..
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