Mucositis is a common toxicity of cancer chemotherapy. Glutamine appears to be the major energy source for intestinal epithelium, and animal studies have suggested that dietary supplementation with glutamine may protect the gut from both radiation and chemotherapy. Patients experiencing stomatitis after a course of chemotherapy were offered the opportunity to enter the current study if no clinical parameters precluded receiving the same chemotherapy doses during the next course of treatment. Patients received the same chemotherapy regimen as during the previous treatment but in addition received a suspension of L-glutamine, 4 gm swish and swallow twice a day, from day 1 of chemotherapy for 28 days or for 4 days past the resolution of any post-chemotherapy mucositis. Twelve patients receiving doxorubicin, 1 receiving etoposide, and 1 receiving ifosfamide, etoposide, and carboplatinum were entered into the study. The maximum grade (CALGB criteria) of mucositis decreased in 12 of 14 patients with glutamine supplementation (median score 2A vs 0.5, p < 0.001). Similarly, after glutamine supplementation, the total number of days of mucositis was decreased in 13 of 14 patients (2.7 ± 0.8 (mean ± SEM) vs 9.9 ± 1.1, p ≥ 0.001). Thirteen of the 14 patients felt that the mucositis was less severe with the addition of glutamine. No change in the nadir neutrophil count was noted with glutamine, and no toxicity of glutamine was observed. We conclude that oral supplementation with glutamine can significantly decrease the severity of chemotherapy-induced stomatitis, an important cause of morbidity in the treatment of patients with cancer. Glutamine supplementation in patients receiving therapy for cancer warrants further study.
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M Ucositis is a common limiting toxicity of cancer chemotherapy. The mechanism of chemotherapy-induced mucositis may be multifactorial. Presumably chemotherapy damages the rapidly dividing immature intestinal crypt cells in the gut and more superficial immature mucosal cells From the Departments of Medicine and Pediatrics, the University of Minnesota Medical School; and the Masonic Center. Supported in part by the Minnesota Medical Foundation (CO-15-91) and by the Vikings Children's Fund. Presented previously in abstract form (Clin Res 1993;41:366A, Proc ASPHO 1993;2:32). Submitted for publication May 19, 1995; revision submitted Sept. 23, 1995; accepted Sept. 26, 1995. Reprint requests: Keith M. Skubitz, MD, Box 325 UMHC, University Hospital, Minneapolis, MN 55455. Copyright © 1996 by Mosby-Year Book, Inc. 0022-2143/96 $5.00 + 0 5/1/69868 in the oropharynx. TM Although perhaps more the result rather than the cause of mucositis, the phenomenon of bacterial translocation across a malfunctioning gut epithelium may also play a role in the gut-related toxicity of chemotherapy and radiotherapy. 3,s,6 Glutamine is the most abundant amino acid in the blood and in the total body amino acid pool, and there has recently been much interest in its role in nutrition (reviewed in references 5 and 7 through 10). Glutamine is a "non-essential" amino acid in that it can be synthesized by most tissues. However, although the metabolism of some tissues such as skeletal muscle and brain yield a net synthesis and export of glutamine, cells of other tissues utilize glutamine as a nitrogen source and also as an energy source\] Glutamine appears to be the major energy source for intestinal epithelium. 7 In addition to be-