Phase 2 Olanzapine dopamine D2/5-HT2A antagonist to prevent weight loss in gastric cancer

This single-center, randomized, open-label Phase 2 supportive-care study at the University of Illinois Cancer Center (University of Illinois Chicago) tests whether adding low-dose olanzapine (2.5 mg by mouth once daily) to standard neoadjuvant chemotherapy improves appetite, limits weight loss, and preserves nutritional status and quality of life in patients with resectable gastric cancer. Olanzapine (originally developed by Eli Lilly; now widely available as a generic) is a small-molecule antagonist at dopamine D2 and serotonin 5-HT2A receptors, a mechanism that has clinical precedent for improving chemotherapy-related nausea and can increase appetite/weight in some settings. Participants are randomized to neoadjuvant chemotherapy alone versus chemotherapy plus olanzapine, starting before chemotherapy and continuing until surgery, with routine monitoring, surgery per usual practice, then follow-up for 2 years. The key angle is “supportive care as an outcome amplifier”: if nutrition and treatment tolerance improve, patients may complete perioperative therapy more reliably without changing the anti-cancer regimen itself. Today’s care for resectable gastric cancer is perioperative multi-agent chemotherapy (commonly FLOT or fluoropyrimidine/platinum-based regimens) followed by gastrectomy ± additional postoperative therapy, and this trial evaluates whether a low-burden adjunct can reduce treatment-associated anorexia and weight loss during the neoadjuvant window.