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• W2067114310 abstract "Lapatinib, the first dual inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) tyrosine kinases, was approved by the US Food and Drug Administration (FDA) in 2007. It is indicated for use in combination with capecitabine for the treatment of patients with advanced breast cancer or metastatic breast cancer (MBC) whose tumors overexpress HER2 (ErbB2) and who have received previous treatment that included an anthracycline, a taxane, and trastuzumab.This review summarizes the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of lapatinib, and its current and potential role in the treatment of breast cancer and other malignancies.Relevant English-language publications were identified through searches of MEDLINE (1966-May 2008),the American Society of Clinical Oncology abstracts database (2000-2007), abstracts from the San Antonio Breast Cancer Symposium (2005-2007), and the FDA Web site (January 2008). Search terms included lapatinib, GW572016, HER2, EGFR, receptor tyrosine kinase, dual-receptor blockade, adverse events, and clinical trials.The T(max) of lapatinib after oral administration is 3 to 4 hours. Dividing the dose or administering it with food, particularly a high-fat meal, increases the AUC >2-fold. Lapatinib is metabolized primarily by the cytochrome P450 3A4 isozyme, with 1 metabolite remaining active against EGFR but not HER2. Due to drug accumulation, the t(1/2) of lapatinib is 24 hours with continuous dosing. In a Phase III trial comparing lapatinib and capecitabine with capecitabine alone in women with HER2-positive, locally advanced breast cancer or MBC that had progressed after treatment with an anthracycline, a taxane, and trastuzumab, the combination of lapatinib and capecitabine was associated with a numeric improvement in response rate compared with capecitabine alone (22% vs 14%, respectively; P = NS) and a significant increase in time to progression (6.2 vs 4.3 months; hazard ratio = 0.57; 95% CI, 0.43-0.77; P < 0.001). Lapatinib has been reported to have antitumor activity in Phase II trials when used as first-line therapy for MBC, in patients with inflammatory breast cancer, and in patients with central nervous system metastases. Phase II trials in other solid tumor types found modest activity. The approved dosing of lapatinib is 1,250 mg PO QD given continuously in combination with capecitabine 2,000 mg/m(2) daily administered in 2 divided doses on days 1 to 14 of a 21-day cycle. The most common clinical toxicities of all grades associated with lapatinib used in combination with capecitabine in the pivotal clinical trial were diarrhea (65%), hand-foot syndrome (53%), nausea (44%), rash (29%), and fatigue (24%). Cardiac toxicity appears to be less frequent with lapatinib than with trastuzumab.Lapatinib is a dual inhibitor of the EGFR and HER2 tyrosine kinases. It is approved by the FDA for use in combination with capecitabine for the treatment of HER2-positive MBC that has progressed with standard treatment. In clinical trials, this combination was associated with a significant improvement in the time to progression in patients with MBC. Lapatinib's efficacy in other malignancies that overexpress EGFR and/or HER2 is under evaluation." @default.
• W2067114310 created "2016-06-24" @default.
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• W2067114310 date "2008-08-01" @default.
• W2067114310 modified "2023-10-02" @default.
• W2067114310 title "Lapatinib: A dual inhibitor of human epidermal growth factor receptor tyrosine kinases" @default.
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• W2067114310 doi "https://doi.org/10.1016/j.clinthera.2008.08.008" @default.
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