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
Notes: Book Chapter -- Export Date: 3 March 2016 -- Source: Scopus
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MSK Authors
  1. Elizabeth Catherine Smyth
    19 Smyth
  2. David H Ilson
    276 Ilson