Chlorpromazine versus Metoclopramide for Neurogenic Nausea and Vomiting in Incurable Patients with Gastrointestinal Tumors: A Prospective Observational Cohort Study.

Background: Nausea and vomiting are prevalent symptoms in incurable patients with gastrointestinal (GI) tumors. While standard antiemetic protocols are widely used, evidence supporting mechanism-based treatment selection in palliative patients remains limited. This study compared outcomes of individualized, mechanism-based antiemetic therapy with standard treatment in this population. Methods: A prospective observational cohort study was conducted at the Palliative Medicine Department of Kyiv City Clinical Oncological Center (2022-2024). In this non-randomized design, treatment was allocated by the treating physician based on clinical judgment of the predominant pathophysiological mechanism. One hundred patients with incurable GI tumors and nausea received standard therapy (metoclopramide plus dexamethasone; n=41) or individualized therapy: ondansetron plus dexamethasone for hepatic-related nausea, or chlorpromazine plus dexamethasone for neurogenic vomiting (n=59). The primary outcome was clinical improvement (≥50% reduction in Visual Analog Scale [VAS] score or vomiting frequency) at day 7. Results: Baseline characteristics were largely comparable between groups (VAS: 7.7±0.9 vs 7.6±0.8, p=0.747; ECOG: 3.8±0.4 vs 3.8±0.4, p=0.635), although hepatic metastases were more prevalent in the individualized group (78.0% vs 51.2%, p=0.005), reflecting mechanism-based allocation. Overall improvement rates were 75.6% (standard) and 88.1% (individualized) (p=0.171). In the neurogenic subgroup, chlorpromazine achieved significantly higher improvement rates than metoclopramide (100% [13/13] vs 55.0% [11/20]; Fisher's exact test, p=0.005), with lower post-treatment VAS scores (4.2±0.6 vs 5.5±0.8; p<0.001). Adverse events were not systematically assessed; however, no treatment discontinuations due to adverse effects were recorded. Conclusion: While overall improvement rates were comparable, chlorpromazine was associated with higher improvement rates than metoclopramide in the neurogenic subgroup. Given the observational, non-randomized design and the small subgroup, these findings are hypothesis-generating and require confirmation in adequately powered randomized controlled trials. They suggest that pathophysiology-guided antiemetic selection, particularly for neurogenic symptoms, warrants further evaluation in palliative GI cancer patients.