Published online Apr 14, 2014. doi: 10.3748/wjg.v20.i14.3905
Revised: December 27, 2013
Accepted: January 20, 2014
Published online: April 14, 2014
Despite advances in the treatment of gastric cancer, it remains the world’s second highest cause of cancer death. As gastric cancer is often diagnosed at an advanced stage, systemic chemotherapy is the mainstay of treatment for these patients. However, no standard palliative chemotherapy regimen has been accepted for patients with metastatic gastric cancer. Palliative chemotherapy including fluoropyrimidine, platin compounds, docetaxel and epirubicin prolongs survival, and improves a high quality of life to a greater extent than best supportive care. The number of clinical investigations associated with targeted agents has recently increased. Agents targeting the epidermal growth factor receptor 1 and human epidermal growth factor receptor 2 (HER2) have been widely tested. Trastuzumab was the first target drug developed, and pivotal phase III trials showed improved survival when trastuzumab was integrated into cisplatin/fluoropyrimidine-based chemotherapy in patients with metastatic gastric cancer. Trastuzumab in combination with chemotherapy was thus approved to be a new standard of care for patients with HER2-positive advanced esophagogastric adenocarcinoma. Thus, the evaluation of HER2 status in all patients with metastatic gastroesophageal adenocarcinoma should be considered. Other agents targeting vascular endothelial growth factor, mammalian target of rapamycin, and other biological pathways have also been investigated in clinical trials, but showed little impact on the survival of patients. In this review, systemic chemotherapy and targeted therapies for metastatic gastric cancer in the first- and second-line setting are summarized in the light of recent advances.
Core tip: Although palliative chemotherapy have been demonstrated to improve survival and quality of life, the prognosis of patients with metastatic gastric cancer remains poor and responses to first-line chemotherapy are partial and heterogeneous. In order to improve the results of currently available treatments, remarkable advancements in new targeted agents have recently been obtained. The addition of trastuzumab to cisplatin/fluoropyrimidine-based chemotherapy significantly improved survival in patients with human epidermal growth factor receptor 2-positive metastatic gastric cancer, which is now the new standard of care. Our manuscript will elucidate current systemic chemotherapy and promising targeted therapies for metastatic gastric cancer in the first- and second-line setting in the light of recent advances.