5-fluorouracil and folinic acid-induced mucositis: no effect of oral glutamine supplementation

Jebb, Susan A.; Osborne, Richard; Maughan, T.S.; Mohideen, Najeeb; Mack, Peter; Mort, D.; Shelley,; Elia, Marinos

doi:10.1038/bjc.1994.385

Cited by 125 publications

(86 citation statements)

References 11 publications

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“…Different observations regarding the efficacy of oral glutamine 15,28 for amelioration of chemotherapy-associated mucositis could be related to different glutamine concentrations in the oral mucosa, as well as the route and schedule of administration. Because of poor solubility and biodistribution, only a suspension can achieve a high local concentration in the oropharynx.…”

Section: Discussionmentioning

confidence: 99%

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Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation

Anderson

Ramsay

Shu

et al. 1998

Bone Marrow Transplant

153

110

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Summary:Painful oral mucositis is a common complication after bone marrow transplantation (BMT). Glutamine is a nutrient for rapidly dividing cells and the major energy source for intestinal epithelium. This study tested whether an oral glutamine preparation could decrease the severity of oral mucositis in patients undergoing BMT. Glutamine or a placebo (glycine) were administered from admission until day +28 in 193 BMT patients in a randomized, double-blind, placebo-controlled study at a dose of 1.0 g amino acid/m 2 /dose swish and swallow four times a day. In autologous BMT patients (n = 87) glutamine was associated with significantly less mouth pain by self report and by opiate use (5.0 ؎ 6.2 days of morphine for glutamine vs 10.3 ؎ 9.8 days for placebo; P = 0.005). Matched sibling BMT patients had no effect by self report and an increased duration of opiate use (23.2 ؎ 5.7 days for glutamine vs 16.3 ؎ 8.3 days for placebo) (P = 0.002). However, day 28 survival of allogeneic patients was improved by glutamine. No significant differences in TPN use, rate of relapse or progression of malignancy, parenteral antibiotic use, acute or chronic GVHD, or days of hospitalization were observed in either autologous or allogeneic recipients. No toxicity of glutamine was observed. We conclude that oral glutamine can decrease the severity and duration of oropharyngeal mucositis in autologous BMT patients but not in allogeneic BMT patients, possibly due to interaction with methotrexate. Keywords: mucositis; stomatitis; supportive care; nutrition; epithelium; chemotherapy Many of the major adverse effects of BMT are related to disruption of mucosal integrity from high-dose chemotherapy and/or radiation-induced damage of oral and intestinal epithelium. Preclinical studies have demonstrated less damage to rat intestinal epithelium if high doses of enteral glutamine were included in the diet during and after 1000 cGy of whole abdominal radiation. [1][2][3] Glutamine is the most abundant amino acid in the blood, but is generally absent Correspondence: Dr P Anderson, Pediatrics-East 9, Mayo Clinic, Rochester, MN 55905, USA Received 7 November 1997; accepted 16 March 1998 from total parenteral nutrition (TPN) for solubility and stability reasons. [4][5][6][7] The intestine utilizes glutamine as its primary energy source, and glutamine has been shown to be an essential dietary component for support and maintenance of intestinal growth and function. 8-10 Supplementation of TPN with glutamine has been shown to decrease villous atrophy associated with exclusive feeding via TPN. 11,12 Nutritionally depleted patients have been shown to have decreased plasma glutamine and mucosal glutamine. 13 Recent studies have also demonstrated a survival advantage of TPN supplementation with glutamine in critically ill patients. 14 Since no information was available concerning the effect of oral glutamine on the squamous epithelium of the oropharynx after chemotherapy and/or radiation, we conducted an earlier pilot study using oral glutamine 4 g/m 2 t...

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Section: Discussionmentioning

confidence: 99%

“…Because of poor solubility and biodistribution, only a suspension can achieve a high local concentration in the oropharynx. If glutamine is either dissolved 28 or given intravenously, 21,29 the concentration in the oral mucosa may be insufficient to significantly ameliorate mucositis and its associated pain.…”

Section: Discussionmentioning

confidence: 99%

Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation

Anderson

Ramsay

Shu

et al. 1998

Bone Marrow Transplant

153

110

View full text Add to dashboard Cite

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“…Bowel ulceration caused by these anti-metabolites and corresponding bacteraemia was reduced (Fox et al, 1988). However, when additional glutamine supplements were given to patients suffering from gastrointestinal cancer, treated by 5-fluorouracil and folinic acid in a placebo-controlled double-blind trial, there was no difference in the degree of observed oral mucositis (Jebb et al, 1994).…”

Section: Anti-ulcer Agentsmentioning

confidence: 99%

Treatment-induced mucositis: an old problem with new remedies

Symonds

1998

Br J Cancer

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Summary Mucositis may be a painful, debilitating, dose-limiting side-effect of both chemotherapy and radiotherapy for which there is no widely accepted prophylaxis or effective treatment. The basis of management is pain relief, prevention of dehydration and adequate nutrition. When tested vigorously, most antiseptic mouthwashes and anti-ulcer agents are ineffective. Simple mechanical cleansing by saline is the most effective traditional measure. A variety of new agents are effective. Granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) act outwith the haemopoeitic system and can reduce mucositis, but the best schedule, dosage and method of administration is not known or which is the best growth factor to prevent this side-effect. A placebo-controlled randomized trial of antibiotic pastilles has shown a significant reduction in mucositis and weight loss during radiotherapy for head and neck cancer. Another method to reduce radiation effects in normal tissue is to stimulate cells to divide before radiotherapy by silver nitrate or interleukin 1. These methods may be particularly effective when given along with hyperfractionated radiation treatment such as CHART.

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“…There is also a reduction in infections with intravenous glutamine. There is, however, an increase in relapse with intravenous Objective Cerchietti et al (12) Daniele et al (13) Huang et al (15) Jebb et al (16) Okuno et al (17) Peterson et al (18) Subtotal (95 % CI) Total events Heterogeneity: χ 2 5.24, df 4 (P=0·26); I 2 24 % Test for overall effect: Z 1·07 (P=0·28) Subjective Huang et al (15) Okuno et al (17) Subtotal (95 % CI) Total events Heterogeneity: χ 2 0·00, df 1 (P=1·00); I 2 0 % Test for overall effect: Z 0·45 (P=0·65) Objective Huang et al (15) Jebb et al (16) Okuno et al (17) Peterson et al (18) Subtotal ( glutamine but this result was based on two small studies (30,32) of patients undergoing autologous transplantation.…”

Section: Bone-marrow Transplantationmentioning

confidence: 99%

Symposium 4: Hot topics in parenteral nutrition A review of the use of glutamine supplementation in the nutritional support of patients undergoing bone-marrow transplantation and traditional cancer therapy

Crowther

2009

Proc. Nutr. Soc.

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The relationship between glutamine and malignancy can be traced back to the 1950s and the requirement for glutamine for malignant-cell growth in culture. Later studies demonstrated an association between the rate of proliferation of the malignant cells and glutamine usage. The excessive use of glutamine by malignant cells was seen as an opportunity for the development of a treatment using glutamine analogues, but unfortunately excessive toxicity was observed during clinical studies. In animal models glutamine supplementation, initially thought to increase tumour growth, actually causes tumour regression as a result of improved immune clearance of the tumour and appears to reduce the severity of the side effects of chemo- and radiotherapy. This finding led to human studies in both traditional cancer therapy and bone-marrow transplantation, which are reviewed here. Unfortunately, the majority of the studies performed are small and have poor methodological reporting. There is clinical heterogeneity in terms of routes of administration, dosing schedules, chemotherapy regimens and diseases. Studies of glutamine in non-bone-marrow transplantation chemo- and/or radiotherapy treatment suggest a possible trend towards reductions in objective mucositis but no effect on subjective symptoms. There is no evidence for its effect on other clinical outcomes. For bone-marrow transplantation there appears to be some benefit from oral glutamine in reducing mucositis and graft v. host disease, while intravenous glutamine may reduce infections but at the expense of an increased relapse rate. Good-quality studies are required in this area.

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5-fluorouracil and folinic acid-induced mucositis: no effect of oral glutamine supplementation

Cited by 125 publications

References 11 publications

Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation

Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation

Treatment-induced mucositis: an old problem with new remedies

Symposium 4: Hot topics in parenteral nutrition A review of the use of glutamine supplementation in the nutritional support of patients undergoing bone-marrow transplantation and traditional cancer therapy

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