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dc.contributor.authorLin, Nancy U
dc.contributor.authorDiéras, Véronique
dc.contributor.authorPaul, Devchand
dc.contributor.authorLossignol, Dominique
dc.contributor.authorChristodoulou, Christos
dc.contributor.authorStemmler, Hans-Joachim
dc.contributor.authorRoché, Henri
dc.contributor.authorLiu, Minetta C
dc.contributor.authorGreil, Richard
dc.contributor.authorCiruelos, Eva
dc.contributor.authorLoibl, Sibylle
dc.contributor.authorGori, Stefania
dc.contributor.authorWardley, Andrew M
dc.contributor.authorYardley, Denise
dc.contributor.authorBrufsky, Adam
dc.contributor.authorBlum, Joanne L
dc.contributor.authorRubin, Stephen D
dc.contributor.authorDharan, Bernie
dc.contributor.authorSteplewski, Klaudia
dc.contributor.authorZembryki, Denise
dc.contributor.authorOliva, Cristina
dc.contributor.authorRoychowdhury, Debasish F
dc.contributor.authorPaoletti, Paolo
dc.contributor.authorWiner, Eric P
dc.date.accessioned2009-06-02T13:58:55Z
dc.date.available2009-06-02T13:58:55Z
dc.date.issued2009-02-15
dc.identifier.citationMulticenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer. 2009, 15 (4):1452-9 Clin. Cancer Res.en
dc.identifier.issn1078-0432
dc.identifier.pmid19228746
dc.identifier.doi10.1158/1078-0432.CCR-08-1080
dc.identifier.urihttp://hdl.handle.net/10541/69595
dc.description.abstractPURPOSE: Brain metastases develop in one third of patients with advanced HER2+ breast cancer. Effective therapy for patients with central nervous system (CNS) progression after cranial radiation is extremely limited and represents a major clinical challenge. Lapatinib, an epidermal growth factor receptor/HER2 inhibitor, was associated with regressions of CNS lesions in a small phase 2 trial. The current study was done to further evaluate the CNS activity of lapatinib. The study was later amended to allow patients who progressed on lapatinib the option of receiving lapatinib plus capecitabine. EXPERIMENTAL DESIGN: Eligible patients had HER2+ breast cancer, progressive brain metastases, prior trastuzumab, and cranial radiotherapy. The primary end point was CNS objective response, defined as >or=50% volumetric reduction of CNS lesion(s) in the absence of increasing steroid use, progressive neurologic signs and symptoms, or progressive extra-CNS disease. RESULTS: Two-hundred and forty-two patients entered the study. CNS objective responses to lapatinib were observed in 6% of patients. In an exploratory analysis, 21% of patients experienced a >or=20% volumetric reduction in their CNS lesions. An association was observed between volumetric reduction and improvement in progression-free survival and neurologic signs and symptoms. Of the 50 evaluable patients who entered the lapatinib plus capecitabine extension, 20% experienced a CNS objective response and 40% experienced a >or=20% volumetric reduction in their CNS lesions. CONCLUSIONS: This study confirms the modest CNS antitumor activity of lapatinib. Additional responses were observed with the combination of lapatinib and capecitabine. Further studies of lapatinib-based regimens for CNS metastases from HER2+ breast cancer are warranted.
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectBrain Canceren
dc.subjectBrain Tumouren
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshAntineoplastic Agents
dc.subject.meshBrain Neoplasms
dc.subject.meshBreast Neoplasms
dc.subject.meshDeoxycytidine
dc.subject.meshFemale
dc.subject.meshFluorouracil
dc.subject.meshHumans
dc.subject.meshMiddle Aged
dc.subject.meshProspective Studies
dc.subject.meshProtein Kinase Inhibitors
dc.subject.meshQuinazolines
dc.subject.meshReceptor, erbB-2
dc.titleMulticenter phase II study of lapatinib in patients with brain metastases from HER2-positive breast cancer.en
dc.typeArticleen
dc.contributor.departmentDana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.en
dc.identifier.journalClinical Cancer Researchen
html.description.abstractPURPOSE: Brain metastases develop in one third of patients with advanced HER2+ breast cancer. Effective therapy for patients with central nervous system (CNS) progression after cranial radiation is extremely limited and represents a major clinical challenge. Lapatinib, an epidermal growth factor receptor/HER2 inhibitor, was associated with regressions of CNS lesions in a small phase 2 trial. The current study was done to further evaluate the CNS activity of lapatinib. The study was later amended to allow patients who progressed on lapatinib the option of receiving lapatinib plus capecitabine. EXPERIMENTAL DESIGN: Eligible patients had HER2+ breast cancer, progressive brain metastases, prior trastuzumab, and cranial radiotherapy. The primary end point was CNS objective response, defined as >or=50% volumetric reduction of CNS lesion(s) in the absence of increasing steroid use, progressive neurologic signs and symptoms, or progressive extra-CNS disease. RESULTS: Two-hundred and forty-two patients entered the study. CNS objective responses to lapatinib were observed in 6% of patients. In an exploratory analysis, 21% of patients experienced a >or=20% volumetric reduction in their CNS lesions. An association was observed between volumetric reduction and improvement in progression-free survival and neurologic signs and symptoms. Of the 50 evaluable patients who entered the lapatinib plus capecitabine extension, 20% experienced a CNS objective response and 40% experienced a >or=20% volumetric reduction in their CNS lesions. CONCLUSIONS: This study confirms the modest CNS antitumor activity of lapatinib. Additional responses were observed with the combination of lapatinib and capecitabine. Further studies of lapatinib-based regimens for CNS metastases from HER2+ breast cancer are warranted.


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