Perioperative adjunctive treatment in the management of operable gastric cancer

Outcome in the management of clinically resectable gastric carcinoma has been disappointing, at least in Western populations, despite increasingly radical surgery and extensive experience with adjunctive perioperative treatment with innumerable single and combined modality regimens. The United States Intergroup Study, a prospective, randomized, controlled trial of adjuvant chemoradiation, demonstrated significant improvement in disease-free and overall survival. Consequently, this regimen of postoperative fluoruracil plus leucovorin and locoregional radiation has been incorporated into current clinical practice. In hopes of further improving cure rates, many other regimens are under investigation, including the efficacy of neoadjuvant therapy alone, combined neoadjuvant and adjuvant therapy, and adjuvant therapy alone. In these clinical trials, therapeutic agents are prescribed alone or in multimodal regimens and include systemic chemotherapy, intraperitoneal (IP) chemotherapy with or without hyperthermia, intraoperative radiotherapy (IORT), and postoperative external beam irradiation. Several molecular markers have been identified, which seem to predict that a given tumor may be effective or resistant to a drug, raising the possibility of customized chemotherapy regimens. Preclinical studies suggest potential efficacy of angiogenesis inhibitors, monoclonal antibodies, and antisense agents.