TY - JOUR
T1 - Effects of glutamine for prevention of radiation-induced esophagitis
T2 - a double-blind placebo-controlled trial
AU - Alshawa, Anas
AU - Cadena, Alexandra Perez
AU - Stephen, Bettzy
AU - Reddy, Akhila
AU - Mendoza, Tito R.
AU - McQuinn, Lacey
AU - Lawhorn, Kristie
AU - Zarifa, Abdulrazzak
AU - Bernhardt, Alexander Maximilian
AU - Fessaheye, Senait
AU - Warneke, Carla L.
AU - Chang, Joe Y.
AU - Naing, Aung
N1 - Funding Information:
Support was provided in part by the National Institutes of Health/National Cancer Institute under award number P30CA016672 (used the Biostatistics Resource Group and the Assessment, Intervention and Measurement (AIM) Facility). Investigational agent glutamine was provided by Healios Oncology Nutrition.
Funding Information:
Dr. Aung Naing: research funding from NCI; EMD Serono; MedImmune; Healios Onc. Nutrition; Atterocor/Millendo; Amplimmune; ARMO BioSciences; Karyopharm Therapeutics; Incyte; Novartis; Regeneron; Merck; BMS; Pfizer, CytomX Therapeutics; Neon Therapeutics; Calithera Biosciences; TopAlliance Biosciences; Eli Lilly; Kymab; PsiOxus; Arcus Biosciences; NeoImmuneTech; ImmuneOncia; Surface Oncology. On advisory board of CytomX Therapeutics, Novartis, Genome & Company, OncoSec KEYNOTE-695 and Kymab. Travel and accommodation expense from ARMO BioSciences.
Publisher Copyright:
© 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8
Y1 - 2021/8
N2 - Purpose Acute radiation-induced esophagitis (ARIE) leads to treatment delays, decreased quality of life (QOL), and secondary adverse events such as weight loss. Grade 3 ARIE occurs in 15%–30% of patients undergoing radiotherapy to the esophagus, leading to disruption or discontinuation of treatment. The purpose of this study was to assess the effects of glutamine, a common nutritional supplement, on ARIE in patients with thoracic malignancies. Patients and methods This double-blind, placebo-controlled trial enrolled patients with advanced thoracic malignancies receiving concurrent chemotherapy/radiotherapy or radiotherapy alone, with radiation doses to the esophagus ≥45 Gy. Patients were randomized (1:1) to receive 4 g of glutamine or glycine placebo twice daily. The primary objective was to determine whether glutamine decreases the severity of ARIE in these patients. Secondary objectives included assessment of the effects of glutamine on other measures of ARIE, weight, symptom burden measure assessed by the MD Anderson Symptom Inventory (MDASI-HN) questionnaire and the toxicity profile of glutamine. Results At the time of interim analysis, 53 patients were enrolled: 27 in the glutamine arm and 26 in the placebo arm. There was no difference in the incidence of esophagitis in the first 6 weeks of radiotherapy between the glutamine and placebo arms (74% versus 68%; P = 1.00). There were no significant differences between the two arms for time to onset of esophagitis. The duration of ARIE was shorter (6.3 versus 7.1 weeks; P = 0.54) and median weight loss was lower (0.9 kg versus 2.8 kg; p = 0.83) in the glutamine arm versus the placebo arm. The groups differ significantly in core symptom severity (2.1 vs 1.5, p <.03) but not in head and neck specific symptom severity (1.2 vs 1.1, p <.60) nor in symptom interference (2.1 vs 1.7, p <.22). There was no grade 3 or higher adverse event at least possibly related to glutamine. The study was terminated for futility following interim analysis. Conclusion Oral glutamine was not associated with significant improvement in severity of ARIE, weight loss, head and neck specific symptoms or symptom interference compared with placebo in patients with advanced thoracic malignancies receiving radiotherapy to the esophagus. Clinical trial information. NCT01952847, and date of registration is September 30, 2013.
AB - Purpose Acute radiation-induced esophagitis (ARIE) leads to treatment delays, decreased quality of life (QOL), and secondary adverse events such as weight loss. Grade 3 ARIE occurs in 15%–30% of patients undergoing radiotherapy to the esophagus, leading to disruption or discontinuation of treatment. The purpose of this study was to assess the effects of glutamine, a common nutritional supplement, on ARIE in patients with thoracic malignancies. Patients and methods This double-blind, placebo-controlled trial enrolled patients with advanced thoracic malignancies receiving concurrent chemotherapy/radiotherapy or radiotherapy alone, with radiation doses to the esophagus ≥45 Gy. Patients were randomized (1:1) to receive 4 g of glutamine or glycine placebo twice daily. The primary objective was to determine whether glutamine decreases the severity of ARIE in these patients. Secondary objectives included assessment of the effects of glutamine on other measures of ARIE, weight, symptom burden measure assessed by the MD Anderson Symptom Inventory (MDASI-HN) questionnaire and the toxicity profile of glutamine. Results At the time of interim analysis, 53 patients were enrolled: 27 in the glutamine arm and 26 in the placebo arm. There was no difference in the incidence of esophagitis in the first 6 weeks of radiotherapy between the glutamine and placebo arms (74% versus 68%; P = 1.00). There were no significant differences between the two arms for time to onset of esophagitis. The duration of ARIE was shorter (6.3 versus 7.1 weeks; P = 0.54) and median weight loss was lower (0.9 kg versus 2.8 kg; p = 0.83) in the glutamine arm versus the placebo arm. The groups differ significantly in core symptom severity (2.1 vs 1.5, p <.03) but not in head and neck specific symptom severity (1.2 vs 1.1, p <.60) nor in symptom interference (2.1 vs 1.7, p <.22). There was no grade 3 or higher adverse event at least possibly related to glutamine. The study was terminated for futility following interim analysis. Conclusion Oral glutamine was not associated with significant improvement in severity of ARIE, weight loss, head and neck specific symptoms or symptom interference compared with placebo in patients with advanced thoracic malignancies receiving radiotherapy to the esophagus. Clinical trial information. NCT01952847, and date of registration is September 30, 2013.
KW - Advanced cancers
KW - Clinical trial
KW - Esophagitis
KW - Glutamine
KW - Prevention
KW - Radiation to the esophagus
KW - Thoracic malignancies
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U2 - 10.1007/s10637-021-01074-w
DO - 10.1007/s10637-021-01074-w
M3 - Article
C2 - 33580845
AN - SCOPUS:85101462090
SN - 0167-6997
VL - 39
SP - 1113
EP - 1122
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 4
ER -