Effect of Immunonutrients on Oral Mucositis in Nasopharyngeal Carcinoma Patients After Chemoradiotherapy

Official title

Efficacy of Immunonutrients in Reducing Oral Mucositis in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: A Prospective, Multicenter, Randomized Controlled Clinical Trial

Overview

The purpose of this study was to investigate the role of immunonutrion compared with standard nutrition in reducing oral mucositis in patients with locally advanced nasopharyngeal carcinoma.

Detailed description

Oral mucositis is the most common adverse reaction in patients with nasopharyngeal carcinoma receiving chemoradiotherapy, of which 40-50% of patients are severe (grade 3-4). Oral mucositis usually results in pain, dysphagia, reduced feeding, and malnutrition. Severe malnutrition in turn increases the risk of severe oral mucositis. Persistent severe oral mucositis will lead to delay and interruption of treatment, impairing patients'quality of life and prognosis. It's reported that nutritional intervention can not only reduce the risk and severity of oral mucositis and improve the nutritional status of patients with head and neck tumors, but also improve patients' tolerance to radiotherapy, quality of life, and prognosis.

Immunonutrition refers to the addition of high content of immune nutrients on the basis of sufficient calories, which not only ensures the supply of nutrition, but also takes into account the effects of anti-inflammation, regulating immunity, improving treatment tolerance, improving prognosis and so on. It has been reported that, comparing with standard enteral nutrition, the incidence of severe oral mucositis and esophagitis in patients with head and neck tumors treated with immunonutrition was lower, suffering less weight loss, and the antitumor immune response was enhanced. The 3-year OS and PFS were significantly improved in patients with good compliance.

It remains to be seen whether or not NPC patients receiving chemoradiotherapy can be benifit from immunonutritional therapy. Therefore, we conducted a prospective, multi-center, randomized controlled clinical study in patients with nasopharyngeal carcinoma who received radiotherapy and chemotherapy without metastases, to further improve the quality of life and prognosis of patients with nasopharyngeal carcinoma.

Interventions

• Dietary supplement Enteral immunonutrition
  Enteral immunonutrition (Oral Impact®, Nestle), 250ml/ bottle, 2 bottles per day, from 5 days before radiotherapy to the end of radiotherapy.
• Dietary supplement Standard enteral nutrition
  Isocaloric standard enteral nutrition formula (ENSURE®)， 250 mL per administration, 3 times per day. Preparation of the 250 mL dose involves adding 200 mL of potable water to a cup and slowly stirring in 52.7 g of ENSURE powder (approximately 6 scoops).

Primary outcome measures

• The incidence of severe oral mucositis [Time frame: 7 weeks]

Secondary outcome measures (12)

• The latency period of severe oral mucositis [Time frame: 7 weeks]
• The duration period of severe oral mucositis [Time frame: 7 weeks]
• Assessment of immune state [Time frame: 4 months]
• Serum hypersensitive C-reactive protein (hsCRP) level [Time frame: 4 months]
• Serum Interleukin-6 (IL-6) level [Time frame: 4 months]
• Hemoglobin level [Time frame: 4 months]
• Serum albumin level [Time frame: 4 months]
• Serum Pre-Albumin level [Time frame: 4 months]
• Nutritional risk [Time frame: 4 months]
• Nutrition status [Time frame: 4 months]
• Physical functional status [Time frame: 4 months]
• overall survival rate (OS) [Time frame: at 2 years after randomisation]

Eligibility criteria

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
• Age 18-70 years old, male or non-pregnant women;
• Pathologically confirmed non-keratinizing carcinoma of the nasopharynx (differentiated or undifferentiated,WHO type II or III);
• Newly diagnosed stage III-IVa (8th AJCC/UICC stage) NPC patients;
• The levels of major organ function meet the following criteria:

(1)Hematology: WBC ≥ 3.0 × 10\^9/L, ANC ≥ 1.5 × 10\^9/L, PLT ≥ 100 × 10\^9/L, HGB ≥ 90 g/L; (2) Liver function: ALT, AST≤2.5 times the upper limit of normal (ULN), total bilirubin ≤ 1.5 × ULN; (3) Renal function: BUN and CRE ≤ 1.5 × ULN or an estimated glomerular filtration rate (eGFR) ≥ 60 ml/min (calculated using the Cockcroft-Gault equation); (4) Adequate coagulation function: defined as an international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times the ULN; (5) Normal levels of cardiac enzymes; 6. The patient has signed informed consent forms and is able to comply with the study's planned visits, treatment plans, and laboratory tests.

Exclusion criteria

• History of investigational Oral Impact®/ENSURE® use within the month prior to enrollment;
• Known allergy or intolerance to any component of investigational Oral Impact®/ENSURE® or related chemotherapy drugs;
• Poor glycemic control in patients with diabetes;
• Patients with autoimmune diseases;
• Patients with active infections;
• Patients who have received radiation therapy or other anti-tumor treatments in the past;
• Patients with a history of other malignant tumors;
• Presence of oral mucositis at baseline;
• Malnutrition at baseline;
• Patients who cannot eat the required amount of food at baseline and require parenteral or enteral nutrition;
• Inability to eat soft solid foods at baseline;
• History of human immunodeficiency virus (HIV) or active hepatitis B/C virus infection;
• Participation in other intervention clinical studies within one month;
• Subjects deemed by the investigator to have other factors that may force them to terminate the study, such as having other serious illnesses (including mental illnesses) that require concomitant treatment, significantly abnormal laboratory test results, or family or social factors that may affect subject safety or data collection.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Supportive care

Study locations

China · 20 centers

• Fujian Provincial Hospital — Fuzhou
• Fujian Cancer Hospital — Fuzhou
• Guangdong Provincial People's Hospital — Guangzhou
• Affiliated Cancer Hospital & Institute of Guangzhou Medical University — Guangzhou
• Huizhou Municipal Central Hospital — Huizhou
• The Affiliated Hospital of Guilin Medical University — Guilin
• Liuzhou Workers Hospital — Liuzhou
• The First Affiliated Hospital of Guangxi Medical University — Nanning
• … and 12 more centers

Publications

• Moslemi D, Nokhandani AM, Otaghsaraei MT, Moghadamnia Y, Kazemi S, Moghadamnia AA. Management of chemo/radiation-induced oral mucositis in patients with head and neck cancer: A review of the current literature. Radiother Oncol. 2016 Jul;120(1):13-20. doi: 10.1016/j.radonc.2016.04.001. Epub 2016 Apr 21. PMID 27113797
• Liang L, Liu Z, Zhu H, Wang H, Wei Y, Ning X, Shi Z, Jiang L, Lin Z, Yan H, Wang R, Hu K. Efficacy and safety of thalidomide in preventing oral mucositis in patients with nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy: A multicenter, open-label, randomized controlled trial. Cancer. 2022 Apr 1;128(7):1467-1474. doi: 10.1002/cncr.34074. Epub 2021 Dec 15. PMID 34910297
• Xia C, Jiang C, Li W, Wei J, Hong H, Li J, Feng L, Wei H, Xin H, Chen T. A Phase II Randomized Clinical Trial and Mechanistic Studies Using Improved Probiotics to Prevent Oral Mucositis Induced by Concurrent Radiotherapy and Chemotherapy in Nasopharyngeal Carcinoma. Front Immunol. 2021 Mar 24;12:618150. doi: 10.3389/fimmu.2021.618150. eCollection 2021. PMID 33841399
• Miyata H, Yano M, Yasuda T, Yamasaki M, Murakami K, Makino T, Nishiki K, Sugimura K, Motoori M, Shiraishi O, Mori M, Doki Y. Randomized study of the clinical effects of omega-3 fatty acid-containing enteral nutrition support during neoadjuvant chemotherapy on chemotherapy-related toxicity in patients with esophageal cancer. Nutrition. 2017 Jan;33:204-210. doi: 10.1016/j.nut.2016.07.004. Epub 2016 PMID 27644137
• Shu Z, Zeng Z, Yu B, Huang S, Hua Y, Jin T, Tao C, Wang L, Cao C, Xu Z, Jin Q, Jiang F, Feng X, Piao Y, Huang J, Chen J, Shen W, Chen X, Wu H, Wang X, Qiu R, Lu L, Chen Y. Nutritional Status and Its Association With Radiation-Induced Oral Mucositis in Patients With Nasopharyngeal Carcinoma During Radiotherapy: A Prospective Study. Front Oncol. 2020 Nov 6;10:594687. doi: 10.3389/fonc.2020.594687. e PMID 33240818
• Kabarriti R, Bontempo A, Romano M, McGovern KP, Asaro A, Viswanathan S, Kalnicki S, Garg MK. The impact of dietary regimen compliance on outcomes for HNSCC patients treated with radiation therapy. Support Care Cancer. 2018 Sep;26(9):3307-3313. doi: 10.1007/s00520-018-4198-x. Epub 2018 Apr 18. PMID 29671062
• Zheng Z, Zhao X, Zhao Q, Zhang Y, Liu S, Liu Z, Meng L, Xin Y, Jiang X. The Effects of Early Nutritional Intervention on Oral Mucositis and Nutritional Status of Patients With Head and Neck Cancer Treated With Radiotherapy. Front Oncol. 2021 Feb 1;10:595632. doi: 10.3389/fonc.2020.595632. eCollection 2020. PMID 33598427
• Boisselier P, Kaminsky MC, Thezenas S, Gallocher O, Lavau-Denes S, Garcia-Ramirez M, Alfonsi M, Cupissol D, de Forges H, Janiszewski C, Geoffrois L, Sire C, Senesse P; Head and Neck Oncology and Radiotherapy Group (GORTEC). A double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX. Am J Clin Nutr. 2020 Dec 10; PMID 32936874

Identifiers

NCT: NCT05892354 · FirstGuangxiMu3

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗