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A phase II study of lapatinib for brain metastases in patients with HER2-overexpressing breast cancer following trastuzumab based systemic therapy and cranial radiotherapy: subset analysis of Japanese patients



A phase II study of lapatinib for brain metastases in patients with HER2-overexpressing breast cancer following trastuzumab based systemic therapy and cranial radiotherapy: subset analysis of Japanese patients



International Journal of Clinical Oncology 18(4): 621-628



It is known that one third of patients with human epidermal growth factor receptor 2 (HER2)-overexpressing metastatic breast cancer (MBC) treated with trastuzumab will develop brain metastases. As the development of brain metastases is fatal, controlling its progression is clinically meaningful. However, effective therapy for MBC patients with brain metastasis after cranial radiation is limited. The international clinical study in which six Japanese patients participated indicated the antitumor activity of lapatinib against brain metastases of HER2-overexpressing breast cancer. The efficacy, safety, and pharmacokinetics of lapatinib 750 mg given twice daily to Japanese HER2-overexpressing MBC patients with brain metastases were assessed as part of the international clinical study. Of six Japanese patients treated in this study, two patients had shown volumetric reduction >20 % in their central nervous system (CNS), one of whom had >50 % reduction. Three patients, including two of these patients, had shown >20 % volumetric reduction in non-CNS lesions. Frequently reported adverse events were diarrhea and rash, all of which were controllable. The AUC0-12 of lapatinib on day 28 was 1.74 times higher than that on day 1. These results suggest that lapatinib monotherapy 750 mg given twice daily can exert some efficacy and has potential as a clinically meaningful treatment option for Japanese HER2-overexpressing breast cancer patients with brain metastases after cranial radiation.

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Accession: 036596526

Download citation: RISBibTeXText

PMID: 23011099

DOI: 10.1007/s10147-012-0444-2


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