Targeted therapies Book Section
| Authors: | Ilson, D. H.; Smyth, E. C. |
| Article/Chapter Title: | Targeted therapies |
| Abstract: | Conventional cytotoxic chemotherapy leads to median survival of less than 1 year for most patients with gastric cancer. Combination chemotherapy is more effective, but is associated with increased toxicity. Most research has focused on agents targeting members of the ERBB/HER family of receptor tyrosine kinases (EGFR, HER2, HER3 and HER4) and components of the angiogenesis pathway, including VEGF and downstream effector tyrosine kinases. Cetuximab, an anti-EGFR monoclonal antibody, has shown modest activity with no excess toxicity in PhaseII studies. Panitumumab, a fully humanized anti-EGFR antibody is currently being evaluated in combination with epirubicin-oxaliplatin-capecitabine chemotherapy in the randomized PhaseIII REAL3 trial. Small-molecule tyrosine kinase inhibitors of the EGF receptor pathway (gefitinib and erlotinib) have not been successful in PhaseII trials in advanced gastric cancer. Trastuzumab, a monoclonal antibody targeting HER2, has been shown in the large randomized PhaseIII TOGA study to improve overall response rate, progression-free survival and overall survival in patients with advanced gastric cancer when combined with cisplatin/5-fluorouracil-based chemotherapy. The small-molecule anti-EGFR/HER2 tyrosine kinase inhibitor lapatinib has not demonstrated efficacy as a single agent in advanced gastric cancer. Bevacizumab, an anti-VEGF monoclonal antibody showed encouraging results in PhaseII nonrandomized US trials, but failed to demonstrate a survival advantage in the worldwide randomized AVAGAST PhaseIII randomized trial. Sorafenib, a small-molecule tyrosine kinase inhibitor targeting angiogenesis has shown activity in the first- and second-line advanced gastric cancer setting, including as a single agent. Gastric cancer may be divided into subtypes based on epidemiology, histology and molecular biology. Gene-expression profiling provides evidence that each of these subtypes may have a unique molecular phenotype that may be exploited in future with targeted agents. © 2011 Future Medicine Ltd. All rights reserved. |
| Book Title: | Management of Advanced Gastric Cancer |
| ISBN: | 9781780841274 |
| Publisher: | Future Medicine |
| Publication Place: | London, UK |
| Date Published: | 2011-11-01 |
| Start Page: | 44 |
| End Page: | 60 |
| Language: | English |
| DOI: | 10.2217/ebo.11.159 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Book Chapter -- Export Date: 3 March 2016 -- Source: Scopus |
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