[Lapatinib treatment-option in trastuzumab-resistant breast cancer].
HER2 is overexpressed in 20-25% of breast cancers and is associated with an aggressive phenotype and poor prognosis. Lapatinib is a dual tyrosine kinase inhibitor selective for inhibition of epidermal growth factor receptor (EGFR1/ErbB1) and HER2/ErbB2. Having more targets, probably its antitumor activity could be more efficient. Preclinical data reveal that lapatinib has activity in trastuzumab-resistant cell lines as well as synergistic activity with trastuzumab. Phase I clinical trials have also shown that lapatinib is well tolerated, with mild diarrhea and skin rush as common toxic effects and low incidence of cardiotoxicity. Lapatinib can cross the blood-brain barrier and might therefore have a role in preventing central-nervous-system progression. In a pivotal phase III trial, a combination of lapatinib and capecitabine almost doubled time to disease progression when compared to capecitabine alone (8.4 vs. 4.1 months) in women with HER2/ErbB2-positive advanced or metastatic breast cancer previously treated with anthracyclin, taxanes and trastuzumab. The overall survival was 15.6 vs. 15.4 months. Several clinical trials that explore the efficacy of lapatinib in combination with conventional chemotherapeutic agents, hormone therapy and other target therapies are ongoing in advanced breast cancer or in neo-adjuvant and adjuvant settings.
Pikó
Béla
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Békés Megyei Képviselôtestület Pándy Kálmán Kórháza Megyei Onkológiai Központ 5700 Gyula Semmelweis u. 1. piko_bhome@freemail.hu
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000517:prevention & control / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D000069287:Capecitabine; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D003875:Drug Eruptions / Q000209:etiology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077341:Lapatinib; D003841:Deoxycytidine; D000069287:Capecitabine; D011505:Protein-Tyrosine Kinases; D000068878:Trastuzumab; D005472:Fluorouracil