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Lapatinib in breast cancer Bilancia D; Rosati G; Dinota A; Germano D; Romano R; Manzione LAnn Oncol 2007[Jun]; 18 Suppl 6 (ä): vi26-30Aberrant activation of some members of human epidermal growth factor receptor (HER) family plays a key role in breast carcinogenesis. Lapatinib is an oral dual tyrosine kinase inhibitor selective for inhibition of epidermal growth factor receptor (EGFR/ErbB1) and HER2/ErbB2. Having more targets, probably its antitumor activity could be more efficient. Clinical data have shown that lapatinib is active in HER2-positive breast cancer as monotherapy, in combination with trastuzumab, and in trastuzumab-resistant patients. Phase I clinical trials have shown also that lapatinib is well tolerated, with mild diarrhea and skin rush as common toxic effects and low incidence of cardiotoxicity. Phase II and III clinical trials' data provide encouraging evidence of the clinical effectiveness of lapatinib in advanced or metastatic breast cancer and for its potential in patients with brain metastases. Interim results from the large, phase III trial in 392 patients showed that in combination with capecitabine lapatinib almost doubled time to progression when compared with capecitabine alone. Several clinical trials that explore the efficacy of lapatinib in combination with conventional chemotherapeutic agents [paclitaxel (Taxol), capecitabine and platinoids], hormonotherapy and other target therapies are ongoing in advanced breast cancer or in neo-adjuvant and adjuvant settings. Our improved understanding of the biology of breast cancer and the use of biomarkers for identification of specific subtypes are allowing us to bring patient-specific novel therapies such as lapatinib to the clinic.|Animals[MESH]|Antineoplastic Agents/adverse effects/pharmacokinetics/pharmacology/*therapeutic use[MESH]|Breast Neoplasms/*drug therapy/metabolism[MESH]|Female[MESH]|Humans[MESH]|Lapatinib[MESH]|Quinazolines/adverse effects/pharmacokinetics/pharmacology/*therapeutic use[MESH]|Randomized Controlled Trials as Topic[MESH] |
