title: Current questions for the treatment of advanced gastric cancer.
abstract: BACKGROUND
  Gastric cancer remains a major health problem worldwide. Treatment of advanced gastric cancer is controversial and there is no standard regimen for first- or second-line chemotherapy (CT). This review aims to give an overview of the hot topics concerning treatment, prognostic factors and new strategies in advanced gastric cancer.
  
  
  METHODS
  Seven questions of special clinical interest have been formulated previously to the literature review. With the aim of answering each of these questions, a specific search of the relevant trials and meta-analyses published or communicated from 1990 to date was performed.
  
  
  RESULTS
  Patients treated with CT have a survival benefit over those treated with only best supportive care (BSC). Such active cytotoxic drugs as cisplatin or docetaxel and targeted agents as trastuzumab showed superiority in randomized trials. Other agents such as oxaliplatin, oral fluoropyrimidines and irinotecan showed non-inferiority or less toxic results, positioning them as valuable alternatives to classical schedules. Combination regimens seem to be an improvement over single agent therapy. However, increased toxicity of some regimens makes their general use difficult. Second-line CT is of value for selected patients with good performance status. Trastuzumab is the only targeted agent showing better survival when added to chemotherapy in HER2-driven tumors.
  
  
  CONCLUSIONS
  With the introduction of new agents, management of advanced gastric cancer has experienced important changes. First and second-line CT improve survival in patients with good performance status. Future trials should address how to better select patients for new, targeted agents, based upon validated predictive biomarkers.
authors.affiliation: Department of Hematology and Medical Oncology, Institute of Health Research INCLIVA, Hospital Clínico Universitario, University of Valencia, Spain. andres.cervantes@uv.es
authors.forename: A
authors.initials: A
authors.lastname: Cervantes
authors.forename: D
authors.initials: D
authors.lastname: Roda
authors.forename: N
authors.initials: N
authors.lastname: Tarazona
authors.forename: S
authors.initials: S
authors.lastname: Roselló
authors.forename: J A
authors.initials: JA
authors.lastname: Pérez-Fidalgo
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D006801:Humans; D058990:Molecular Targeted Therapy; D016032:Randomized Controlled Trials as Topic; D013274:Stomach Neoplasms / Q000188:drug therapy*; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068878:Trastuzumab