Effects of glutamine for prevention of radiation-induced esophagitis: a double-blind placebo-controlled trial

• Published in: Investigational new drugs 2021-08, Vol.39 (4), p.1113-1122
• Main Authors: Alshawa, Anas, Cadena, Alexandra Perez, Stephen, Bettzy, Reddy, Akhila, Mendoza, Tito R., McQuinn, Lacey, Lawhorn, Kristie, Zarifa, Abdulrazzak, Bernhardt, Alexander Maximilian, Fessaheye, Senait, Warneke, Carla L., Chang, Joe Y., Naing, Aung
• Format: Article
• Language: English
• Subjects: Adverse events; Aged; Antineoplastic Agents - administration & dosage; Chemotherapy; Clinical trials; Combined Modality Therapy; Double-Blind Method; Double-blind studies; Esophagitis; Esophagitis - epidemiology; Esophagitis - etiology; Esophagitis - prevention & control; Esophagus; Female; Glutamine; Glutamine - administration & dosage; Glutamine - adverse effects; Glycine; Head and neck; Humans; Incidence; Interference; Lung cancer; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Patients; Pharmacology/Toxicology; Phase III Studies; Placebos; Quality of life; Radiation; Radiation dosage; Radiation effects; Radiation Injuries - epidemiology; Radiation Injuries - prevention & control; Radiation therapy; Severity of Illness Index; Thoracic Neoplasms - radiotherapy; Thorax; Time Factors; Toxicity; Weight loss
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-021-01074-w

Summary 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