| Lapatinib (INN) or lapatinib ditosylate (USAN), also known as
GW572016, is an anti-cancer drug developed by GlaxoSmithKline (GSK) as a treatment for
solid tumours such as breast and lung cancer. It was approved by the FDA on March 13,
2007, for use in patients with advanced metastatic breast cancer in conjunction with the
chemotherapy drug Capecitabine (Xeloda TM). It is marketed by GSK in the U.S. as
Tykerb
and in Europe as Tycerb. Lapatinib is a once-daily oral drug indicated for women who have received prior treatment with the intravenous drug Trastuzumab (Herceptin TM) and cancer drugs called taxanes and anthracyclines. Lapatinib is an epidermal growth factor receptor (EGFR) and HER2/neu (ErbB-2) dual tyrosine kinase inhibitor. It binds to the intracellular phosphorylation domain to prevent receptor autophospohorylation upon ligand binding. The exact site of binding has currently not been confirmed (EGFR and ErbB2 have a number of intracellular phosphorylation sites). In patients with HER2+ metastatic breast cancer that has progressed following treatment with regimens that included an anthracycline, a taxane, and trastuzumab; randomized clinical trial has demonstrated that the addition of lapatinib to capecitabine delayed the time of further cancer growth compared to capecitabine alone. Go here for more The Food and Drug Administration (2010) has expanded the approval for Tykerb (lapatinib), to now be used in combination with letrozole (Femara) for hormone-positive and HER2-positive advanced breast cancer in postmenopausal women for whom hormonal therapy is indicated. “This drug combination of Tykerb plus Femara provides women being treated for advanced breast cancer with an important treatment option. This entirely oral treatment regimen works by targeting both HER2 and the hormone receptors, thereby slowing the cancer cells’ ability to grow or spread,” Richard Pazdur, MD, the Director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, said in a news release. Women with HER2-positive breast cancer receiving the combination more than doubled the time they lived without the cancer progressing compared with those receiving letrozole alone (35 vs 13 weeks). Women in the company-sponsored study were randomized to receive lapatinib + letrozone or letrozone alone. It is too early to determine whether an improvement in overall survival will be observed in the clinical trial, the news release notes. Lapatinib works by depriving tumor cells of signals needed to grow; lapatinib enters the cell and blocks the function of the HER2 protein. Tykerb was initially approved in combination with Xeloda (capecitabine) in 2007. This combination was used to treat women with advanced breast cancer tumors with the HER2 protein who had received prior treatment with chemotherapy drugs, including an anthracycline and a taxane, and trastuzumab. Safety information from this study was consistent with previous lapatinib clinical studies in advanced breast cancer. The most commonly reported side effects of the combination were diarrhea, rash, nausea, and fatigue. Treatment with lapatinib has also been associated with decreased heart function, liver damage, and lung tissue inflammation. Fetal harm may occur if the drug is used to treat advanced breast cancer in pregnant women. Tykerb is marketed by GlaxoSmithKline, and Femara, by Novartis AG.
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