Development of targeted therapies in advanced gastric cancer: promising exploratory steps in a new era.
OBJECTIVE
Many chemotherapeutic drugs, including fluoropyrimidines, platinums, CPT-11, taxanes and adriamycin have single-agent activity in advanced gastric cancer. Although combination chemotherapy has been shown to be more effective than single agents, response rates between 30 and 50% have not fulfilled their promise as progression-free survival from the best combinations ranges between 3 and 7 months and overall survival between 8 and 11 months. The development of targeted therapies in gastric cancer clearly stays behind the integration of these novel agents into new treatment concepts for patients with colorectal cancer. This review summarizes the experience and major recent advances in the development of targeted therapies in advanced gastric cancer.


RESULTS
Recent publications on targeted therapies in gastric cancer are limited to nonrandomized phase I or II trials. The majority of agents tested were angiogenesis inhibitors or agents targeting the epidermal growth factor receptors epidermal growth factor receptor 1 and HER2.


CONCLUSIONS
Adequately powered, randomized phase III trials are necessary to define the clinical role of targeted therapies in advanced gastric cancer. Biomarker studies to correlate with treatment outcomes will be critical to identify patients who benefit most from chemotherapy and targeted therapy.
Multidisciplinary Oncology Center, Lausanne University Hospital, Lausanne, Switzerland. dorothea.wagner@chuv.ch
Anna D
AD
Wagner
Markus
M
Moehler
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D013274:Stomach Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000201:enzymology
D020533:Angiogenesis Inhibitors; D066246:ErbB Receptors; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases