The usefulness of immunonutrition in chemotherapy and chemoradiotherapy for esophageal cancer

Araki,Satomi; Araki,Takuya; Tanaka,Naritaka; Sakai,Makoto; Nagamine,Ayumu; Nagano,Daisuke; Yashima,Hideaki; Saeki,Hiroshi; Kuwano,Hiroyuki; Yamamoto,Koujirou

doi:10.3892/ol.2025.15174

The usefulness of immunonutrition in chemotherapy and chemoradiotherapy for esophageal cancer

Authors:
- Satomi Araki
- Takuya Araki
- Naritaka Tanaka
- Makoto Sakai
- Ayumu Nagamine
- Daisuke Nagano
- Hideaki Yashima
- Hiroshi Saeki
- Hiroyuki Kuwano
- Koujirou Yamamoto
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Affiliations: Department of Clinical Pharmacology and Therapeutics, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Division of Gastroenterological Surgery, Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371‑8511, Japan, Department of Pharmacy, Gunma University Hospital, Maebashi, Gunma 371‑8511, Japan, Regional Comprehensive Support Center, Okagaki Hospital, Onga, Fukuoka 811‑4204, Japan
Published online on: July 7, 2025 https://doi.org/10.3892/ol.2025.15174
Article Number: 428

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Abstract

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.

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1	Lyman GH, Dale DC and Crawford J: Incidence and predictors of low Dose-intensity in adjuvant breast cancer chemotherapy: A nationwide study of community practices. J Clin Oncol. 21:4524–4531. 2003. View Article : Google Scholar
2	Lyman GH, Dale DC, Friedberg J, Crawford J and Fisher RI: Incidence and predictors of low chemotherapy Dose-intensity in aggressive non-Hodgkin's lymphoma: A nationwide study. J Clin Oncol. 22:4302–4311. 2004. View Article : Google Scholar
3	Kuderer NM, Dale DC, Crawford J, Cosler LE and Lyman GH: Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer. 106:2258–2266. 2006. View Article : Google Scholar : PubMed/NCBI
4	Sakai M, Sohda M, Uchida S, Yamaguchi A, Watanabe T, Saito H, Ubukata Y, Nakazawa N, Kuriyama K, Sano A, et al: Concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-Fluorouracil (DCF-RT) for patients with potentially resectable esophageal cancer. Anticancer Res. 42:4929–4935. 2022. View Article : Google Scholar : PubMed/NCBI
5	Miyazaki T, Ojima H, Fukuchi M, Sakai M, Sohda M, Tanaka N, Suzuki S, Ieta K, Saito K, Sano A, et al: Phase II study of docetaxel, nedaplatin, and 5-Fluorouracil combined chemotherapy for advanced esophageal cancer. Ann Surg Oncol. 22:3653–3658. 2015. View Article : Google Scholar
6	Ponton F, Wilson K, Cotter SC, Raubenheimer D and Simpson SJ: Nutritional immunology: A Multi-dimensional approach. PLoS Pathog. 7:e10022232011. View Article : Google Scholar : PubMed/NCBI
7	Bourke CD, Berkley JA and Prendergast AJ: Immune dysfunction as a cause and consequence of malnutrition. Trends Immunol. 37:386–398. 2016. View Article : Google Scholar
8	Ravasco P, Monteiro-Grillo I, Vidal PM and Camilo ME: Cancer: Disease and nutrition are key determinants of patients' quality of life. Support Care Cancer. 12:246–252. 2004. View Article : Google Scholar : PubMed/NCBI
9	Sachlova M, Majek O and Tucek S: Prognostic value of scores based on malnutrition or systemic inflammatory response in patients with metastatic or recurrent gastric cancer. Nutr Cancer. 66:1362–1370. 2014. View Article : Google Scholar : PubMed/NCBI
10	Ni J and Zhang L: Cancer cachexia: Definition, staging, and emerging treatments. Cancer Manag Res. 12:5597–5605. 2020. View Article : Google Scholar : PubMed/NCBI
11	Meng L, Wei J, Ji R, Wang B, Xu X, Xin Y and Jiang X: Effect of early nutrition intervention on advanced nasopharyngeal carcinoma patients receiving chemoradiotherapy. J Cancer. 10:3650–3656. 2019. View Article : Google Scholar : PubMed/NCBI
12	Prado CM, Laviano A, Gillis C, Sung AD, Gardner M, Yalcin S, Dixon S, Newman SM, Bastasch MD, Sauer AC, et al: Examining guidelines and new evidence in oncology nutrition: A position paper on gaps and opportunities in multimodal approaches to improve patient care. Support Care Cancer. 30:3073–3083. 2022. View Article : Google Scholar : PubMed/NCBI
13	Akcam TI, Tekneci AK, Kavurmaci O, Ozdil A, Ergonul AG, Turhan K, Cakan A and Cagirici U: The significance of immunonutrition nutritional support in patients undergoing postoperative adjuvant chemotherapy for lung cancer: Case-control study. World J Surg Oncol. 21:1832023. View Article : Google Scholar
14	Calder PC: n-3 PUFA and inflammation: From membrane to nucleus and from bench to bedside. Proc Nutr Soc. 1–13. June 22–2020.(Epub ahead of print). View Article : Google Scholar
15	Kubota H, Matsumoto H, Higashida M, Murakami H, Nakashima H, Oka Y, Okumura H, Yamamura M, Nakamura M and Hirai T: Eicosapentaenoic acid modifies cytokine activity and inhibits cell proliferation in an oesophageal cancer cell line. Anticancer Res. 33:4319–4324. 2013.PubMed/NCBI
16	Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W and Dennison A: The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Eur J Cancer. 45:2077–2086. 2009. View Article : Google Scholar : PubMed/NCBI
17	Fang X, Ge K, Song C, Ge Y and Zhang J: Effects of n-3PUFAs on autophagy and inflammation of hypothalamus and body weight in mice. Biochem Biophys Res Commun. 501:927–932. 2018. View Article : Google Scholar : PubMed/NCBI
18	Chiang N and Serhan CN: Specialized pro-resolving mediator network: An update on production and actions. Essays Biochem. 64:443–462. 2020. View Article : Google Scholar : PubMed/NCBI
19	Goldberg RJ and Katz J: A Meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 129:210–223. 2007. View Article : Google Scholar : PubMed/NCBI
20	Zhao Y and Wang C: Effect of ω-3 polyunsaturated fatty acid-supplemented parenteral nutrition on inflammatory and immune function in postoperative patients with gastrointestinal malignancy: A meta-analysis of randomized control trials in China. Medicine. 97:e04722018. View Article : Google Scholar : PubMed/NCBI
21	Song GM, Tian X, Zhang L, Ou YX, Yi LJ, Shuai T, Zhou JG, Zeng Z and Yang HL: Immunonutrition support for patients undergoing surgery for gastrointestinal malignancy: Preoperative, postoperative, or perioperative? A Bayesian network Meta-analysis of randomized Controlled Trials. Medicine (Baltimore). 94:e12252015. View Article : Google Scholar : PubMed/NCBI
22	Probst P, Ohmann S, Klaiber U, Hüttner FJ, Billeter AT, Ulrich A, Büchler MW and Diener MK: Meta-analysis of immunonutrition in major abdominal surgery: Immunonutrition in major abdominal surgery. Br J Surg. 104:1594–1608. 2017. View Article : Google Scholar : PubMed/NCBI
23	Miyata H, Yano M, Yasuda T, Yamasaki M, Murakami K, Makino T, Nishiki K, Sugimura K, Motoori M, Shiraishi O, et al: Randomized study of the clinical effects of ω-3 fatty acid-containing enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer. Nutrition. 33:204–210. 2017. View Article : Google Scholar : PubMed/NCBI
24	Akita H, Takahashi H, Asukai K, Tomokuni A, Wada H, Marukawa S, Yamasaki T, Yanagimoto Y, Takahashi Y, Sugimura K, et al: The utility of nutritional supportive care with an eicosapentaenoic acid (EPA)-enriched nutrition agent during pre-operative chemoradiotherapy for pancreatic cancer: Prospective randomized control study. Clin Nutr ESPEN. 33:148–153. 2019. View Article : Google Scholar : PubMed/NCBI
25	Miller LJ, Douglas C, McCullough FS, Stanworth SJ and Calder PC: Impact of enteral immunonutrition on infectious complications and immune and inflammatory markers in cancer patients undergoing chemotherapy: A systematic review of randomised controlled trials. Clin Nutr. 41:2135–2146. 2022. View Article : Google Scholar : PubMed/NCBI
26	Prieto I, Montemuiño S, Luna J, de Torres MV and Amaya E: The role of immunonutritional support in cancer treatment: Current evidence. Clin Nutr. 36:1457–1464. 2017. View Article : Google Scholar : PubMed/NCBI
27	Vasson M P, Talvas J, Perche O, Dillies AF, Bachmann P, Pezet D, Achim AC, Pommier P, Racadot S, Weber A, et al: Immunonutrition improves functional capacities in head and neck and esophageal cancer patients undergoing radiochemotherapy: A randomized clinical trial. Clin Nutr. 33:204–210. 2014. View Article : Google Scholar : PubMed/NCBI
28	Lee JLC, Leong LP and Lim SL: Nutrition intervention approaches to reduce malnutrition in oncology patients: A systematic review. Support Care Cancer. 24:469–480. 2016. View Article : Google Scholar : PubMed/NCBI
29	de van der Schueren MAE, Laviano A, Blanchard H, Jourdan M, Arends J and Baracos VE: Systematic review and meta-analysis of the evidence for oral nutritional intervention on nutritional and clinical outcomes during chemo(radio)therapy: Current evidence and guidance for design of future trials. Ann Oncol. 29:1141–1153. 2018. View Article : Google Scholar
30	Chitapanarux I, Traisathit P, Chitapanarux T, Jiratrachu R, Chottaweesak P, Chakrabandhu S, Rasio W, Pisprasert V and Sripan P: Arginine, glutamine, and fish oil supplementation in cancer patients treated with concurrent chemoradiotherapy: A randomized control study. Curr Probl Cancer. 44:1004822020. View Article : Google Scholar : PubMed/NCBI
31	Bonatto SJ, Oliveira HH, Nunes EA, Pequito D, Iagher F, Coelho I, Naliwaiko K, Kryczyk M, Brito GA, Repka J, et al: Fish oil supplementation improves neutrophil function during cancer chemotherapy. Lipids. 47:383–389. 2012. View Article : Google Scholar : PubMed/NCBI
32	Hwang HS, Yoon DH, Suh C and Huh J: Body mass index as a prognostic factor in Asian patients treated with chemoimmunotherapy for diffuse large B-cell lymphoma, not otherwise specified. Ann Hematol. 94:1655–1665. 2015. View Article : Google Scholar
33	Chen S, Chen CM, Zhou Y, Zhou RJ, Yu KD and Shao ZM: Obesity or overweight is associated with worse pathological response to neoadjuvant chemotherapy among Chinese women with breast cancer. PLoS One. 7:e413802012. View Article : Google Scholar : PubMed/NCBI
34	Murakami K, Miyata H, Miyazaki Y, Makino T, Takahashi T, Kurokawa Y, Yamasaki M, Nakajima K, Takiguchi S, Mori M and Doki Y: ω-3 Fatty acids reduce Chemotherapy-induced hematological toxicity by bone marrow stimulation in mice. JPEN J Parenter Enteral Nutr. 41:815–823. 2017. View Article : Google Scholar : PubMed/NCBI
35	Cao D, Kevala K, Kim J, Moon HS, Jun SB, Lovinger D and Kim HY: Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. J Neurochem. 111:510–521. 2009. View Article : Google Scholar : PubMed/NCBI
36	Tomasdottir V, Thorleifsdottir S, Vikingsson A, Hardardottir I and Freysdottir J: Dietary omega-3 fatty acids enhance the B1 but not the B2 cell immune response in mice with antigen-induced peritonitis. J Nutr Biochem. 25:111–117. 2014. View Article : Google Scholar : PubMed/NCBI
37	Hou TY, McMurray DN and Chapkin RS: Omega-3 fatty acids, lipid rafts, and T cell signaling. Eur J Pharmacol. 785:2–9. 2016. View Article : Google Scholar
38	Katakura M, Hashimoto M, Okui T, Shahdat HM, Matsuzaki K and Shido O: Omega-3 polyunsaturated Fatty acids enhance neuronal differentiation in cultured rat neural stem cells. Stem Cells Int. 2013:4904762013. View Article : Google Scholar