Long-term clinical response in leptomeningeal metastases from breast cancer treated with capecitabine monotherapy: a case report.
ABSTRACT Brain and leptomeningeal metastases from breast cancer carry a poor prognosis and are often less responsive to systemic therapy. It is often thought that systemic therapy has a minimal role in the management of central nervous system (CNS) metastases because of the impermeability of the blood-brain barrier. However, treatments directed to the CNS such as radiation or intrathecal chemotherapy are not effective in managing concurrent non-CNS metastases. We report the long-term control of a woman receiving capecitabine with brain and leptomeningeal metastases. After 3.7 years of capecitabine therapy after whole-brain radiation, the patient remains without neurologic symptoms or deficits, has no evidence of disease on neuroimaging studies, but has a persistent positive cytology. This case report demonstrates that, in principle, systemic therapy can provide long-term complete responses for some patients with CNS metastases. The significance of persistent circulating tumor cells in the CNS in patients without evidence of disease is unclear but should be investigated further.
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ABSTRACT: The management of patients with brain metastases from breast cancer continues to be a major clinical challenge. The standard initial therapeutic approach depends upon the size, location, and number of metastatic lesions and includes consideration of surgical resection, whole-brain radiotherapy, and stereotactic radiosurgery. As systemic therapies for control of extracranial disease improve, patients are surviving long enough to experience subsequent progression events in the brain. Therefore, there is an increasing need to identify both more effective initial treatments as well as to develop multiple lines of salvage treatments for patients with breast cancer brain metastases. This review summarises the clinical experience to date with respect to cytotoxic and targeted systemic therapies for the treatment of brain metastases, highlights ongoing and planned trials of novel approaches and identifies potential targets for future investigation.ecancermedicalscience 01/2013; 7:307.
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ABSTRACT: Leptomeningeal metastasis (LM) results from metastatic spread of cancer to the leptomeninges, giving rise to central nervous system dysfunction. Breast cancer, lung cancer, and melanoma are the most frequent causes of LM among solid tumors in adults. An early diagnosis of LM, before fixed neurologic deficits are manifest, permits earlier and potentially more effective treatment, thus leading to a better quality of life in patients so affected. Apart from a clinical suspicion of LM, diagnosis is dependent upon demonstration of cancer in cerebrospinal fluid (CSF) or radiographic manifestations as revealed by neuraxis imaging. Potentially of use, though not commonly employed, today are use of biomarkers and protein profiling in the CSF. Symptomatic treatment is directed at pain including headache, nausea, and vomiting, whereas more specific LM-directed therapies include intra-CSF chemotherapy, systemic chemotherapy, and site-specific radiotherapy. A special emphasis in the review discusses novel agents including targeted therapies, that may be promising in the future management of LM. These new therapies include anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib in nonsmall cell lung cancer, anti-HER2 monoclonal antibody trastuzumab in breast cancer, anti-CTLA4 ipilimumab and anti-BRAF tyrosine kinase inhibitors such as vermurafenib in melanoma, and the antivascular endothelial growth factor monoclonal antibody bevacizumab are currently under investigation in patients with LM. Challenges of managing patients with LM are manifold and include determining the appropriate patients for treatment as well as the optimal route of administration of intra-CSF drug therapy.Surgical Neurology International 01/2013; 4(Suppl 4):S265-S288. · 1.18 Impact Factor
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ABSTRACT: In patients with breast cancer with overexpression of the HER2 receptor, during treatment with trastuzumab, in 30% of cases brain metastases are observed. The use of lapatinib with capecitabine (L + C) seems to be an efficacious method of curing patients in whom the spread of cancer in this location has occurred. In a patient aged 52 treated by the L + C scheme a stabilization of changes in the brain was noted, lingering for 17 months. The tolerance of the treatment was good. Grade 2 hand-foot syndrome on the NCI 2,0 scale, nausea, a first degree increase in transaminase levels and first degree diarrhea were observed. No hematological or cardiac complications were observed. In the third phase test comparing capecitabine with capecitabine and lapatinib in patients with advanced breast cancer, adding lapatinib to capecitabine significantly prolonged the time until progression and contributed to lessening of the amount of progression of the condition into the central nervous system. Recently published studies showed 6% remission of metastases to the central nervous system in patients with advanced breast cancer with brain metastases treated with lapatinib and 20-21% in patients receiving lapatinib with capecitabine. Future studies evaluating the effectiveness of lapatinib in patients with spread into the central nervous system should include the evaluation of lapatinib in association with cytostatics able to break through the blood-brain barrier. Lapatinib should also be tested in association with brain radiation, considering the results of preclinical studies indicating that it may work as a radiation sensitizer.Contemporary Oncology / Wspólczesna Onkologia 01/2012; 16(6):582-585. · 0.22 Impact Factor