The usefulness of immunonutrition in chemotherapy and chemoradiotherapy for esophageal cancer.

Reducing the risk of infections associated with myelosuppression, particularly neutropenia, is crucial for ensuring chemotherapy completion and maximizing efficacy. Oral immunonutrition (OIN) containing omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has garnered attention. While OIN can reduce postoperative infections and improve prognosis, its impact on chemotherapy and chemoradiotherapy completion rates in esophageal cancer remains unclear. Therefore, retrospective and prospective (UMIN000056761) studies were conducted to evaluate the effects of OIN in patients undergoing chemotherapy or chemoradiotherapy for esophageal cancer. In the retrospective study, 32 patients were analyzed: 15 in the docetaxel, nedaplatin and 5-fluorouracil (DNF) group (OIN, 6; control, 9) and 17 in the docetaxel, cisplatin and 5-fluorouracil (DCF) with radiotherapy (DCF-RT) group (OIN, 7; control, 10). Although OIN (ProSure) did not significantly affect the completion rates of the DNF regimen (P=0.622), it significantly improved the second-cycle completion rate of the DCF-RT regimen (P=0.030). In addition, although OIN had no significant effect on febrile neutropenia or other adverse events, except for nausea in the DNF group, first-cycle granulocyte colony-stimulating factor (G-CSF) use was significantly lower in the OIN group (P=0.001). In the prospective study, 14 patients were studied. Due to the small sample size, the primary endpoint could not be evaluated; however, OIN significantly increased the plasma-free EPA/arachidonic acid (AA) ratio on days 3 and 7 (both P=0.011), whereas the free DHA/AA ratio remained unchanged. These findings suggested that increasing the EPA/AA ratio via OIN may contribute to immune activation in cancer chemotherapy, leading to reduced G-CSF use and improved treatment completion rates. Although based on a limited number of patients, these results provide pilot evidence supporting the immunonutritional potential of OIN in esophageal cancer treatment. The prospective study (UMIN000056761) was retrospectively registered on January 21, 2025.