Role of oral glutamine in alleviation and prevention of radiation-induced oral mucositis: A prospective randomized study

Subrata Chattopadhyay; Aramita Saha; Mohammad Azam; Anindya Mukherjee; Prabir Kumar Sur

doi:10.4103/2278-330X.126501

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QUEST FOR AN ANTIDOTE TO RADIATION TOXICITY : Original Article

03 (

); 008-012

doi:

10.4103/2278-330X.126501

Role of oral glutamine in alleviation and prevention of radiation-induced oral mucositis: A prospective randomized study

Subrata Chattopadhyay¹, Aramita Saha^1,, Mohammad Azam¹, Anindya Mukherjee¹, Prabir Kumar Sur^1,2

1 Department of Radiotherapy, Medical College, Kolkata, West Bengal

2 Department of Clinical Oncology, Hemalata Hospitals and Research Center, Bhubaneswar, Orissa

*Corresponding author: Dr. Aramita Saha. docaramita@gmail.com

Published: 2020-12-31

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Abstract

Background: Oral mucositis is the most frequently occurring painful and dose-limiting side-effect of radiation of the head and neck region. Few studies demonstrated that oral glutamine suspension may significantly reduce the duration and severity of objective oral mucositis during radiotherapy. Materials and Methods: A randomized, prospective single institutional case control study was performed between April 2012 and November 2012 comparing the influence of oral glutamine on radiation induced mucositis in head and neck malignancy patients. Seventy biopsy proven patients with head and neck cancer receiving primary or adjuvant radiation therapy were randomized to receive either oral glutamine suspension daily 2h before radiation in the study arm (10 g in 1000 ml of water) (n = 35) or nothing before radiation; control arm (n = 35). Results and Analysis: Total 32 patients (91.43%) in the glutamine arm and total 34 patients (97.15%) developed mucositis. Grade 3 mucositis (14.29%) and grade 4 mucositis (2.86%) in the study arm (who received oral glutamine) were significantly less (P = 0.02 and P = 0.04, respectively) in the glutamine arm. The mean duration of grade 3 or worse mucositis (grade 3 and grade 4) was significantly less (6.6 days vs. 9.2 days) in study arm with P < 0.001. Mean time of onset of mucositis was significantly delayed in patients who took glutamine in comparison to control arm with P < 0.001. Conclusion: Glutamine delays oral mucositis in the head neck cancer patients. Moreover, it reduces the frequency and duration of grade 3 and grade 4 mucositis.

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References

Dose AM. The symptom experience of mucositis, stomatitis, and xerostomia. Semin Oncol Nurs 1995;11:248-55.
Zlotolow IM. General consideration in prevention and treatment of oral manifestation of cancer therapies. In: Berget AP, Weissman DE, editors. Principles and Practice of Supportive Oncology. Philadelphia, PA: Lippincott Raven; 1998. p. 237.
Vissink A, Jansma J, Spijkervet FK, Burlage FR, Coppes RP. Oral sequele of head and neck radiotherapy. Crit Rev Oral Biol Med 2003;14:199-212.
Lee DJ, Cosmatos D, Marcial VA, Fu KK, Rotman M, Cooper JS, et al. Results of an RTOG phaseIII trial (RTOG 85-27) comparing radiotherapy plus etanidazole with radiotherapy alone for locally advanced head and neck carcinomas. Int J Radiat Oncol Biol Phys 1995;32:567-76.
Fu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL, et al. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: First report of RTOG 9003. Int J Radiat Oncol Biol Phys 2000;48:7-16.
Bitran JD, Samuels B, Klein L, Hanauer S, Johnson L, Martinec J, et al. Tandem high-dose chemotherapy supported by hematopoietic progenitor cells yields prolonged survival in stage IV breast cancer. Bone Marrow Transplant 1996;17:157-62.
Mead G M. Management of oral mucositis associated with cancer chemotherapy. Lancet 2002;359:815-6.
Krebs H. Glutamine metabolism in the anima lbody. In: Mora J, Palacios R, editors. Glutamine: Metabolism, enzymology and regulation. NewYork: Academic Press; 1980. p. 319-25.
Windmueller HG, Spaeth AE. Uptake and metabolism of plasma glutamine by the small intestine. J Biol Chem 1974;249:5070-9.
Windmueller HG, Spaeth AE. Identification of ketone bodies and glutamine as the major respiratory fuels in vivo for post absorptive rat small intestine. J Biol Chem 1978;253:69-76.
Baskerville A, Hambleton P, Benbough JE. Pathological features of glutaminase toxicity. Br J Exp Pathol 1980;61:132-8.
Rouse K, Nwokedi E, Woodliff JE, Epstein J, Klimberg VS. Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism. Ann Surg 1995;221:420-6.
Savarese DM, Savy G, Vahdat L, Wischmeyer PE, Corey B. Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treat Rev 2003;29:501-13.
Klimberg VS, Kornbluth J, Cao Y, Dang A, Blossom S, Schaeffer RF. Glutamine suppresses PGE 2 synthesis and breast cancer growth. J Surg Res 1996;63:293-7.
Shewchuk LD, Baracos VE, Field CJ. Dietary L-glutamine supplementation reduces the growth of the Morris Hepatoma7777 in exercise-trained and sedentary rats. J Nutr 1997;127:158-66.
Ardawi MS, Newsholme EA. Glutamine metabolism in lymphocytes of the rat. Biochem J 1983;212:835-42.
Klimberg VS, Souba WW, Dolson DJ, Salloum RM, Hautamaki RD, Plumley DA, et al. Prophylactic glutamine protects the intestinal mucosa from radiation injury. Cancer 1990;66:62-8.
Huang EY, Leung SW, Wang CJ, Chen HC, Sun LM, Fang FM, et al. Oral glutamine to alleviate radiation-induced oral mucositis: A pilot randomized trial. Int J Radiat Oncol Biol Phys 2000;46:535-9.
Silverman S Jr. Diagnosis and management of oral mucositis. J Support Oncol 2007;5(Suppl 1):13-21.
Billings RJ, Proskin HM, Moss ME. Xerostomia and associated factors in a community-dwelling adult population. Community Dent Oral Epidemiol 1996;24:312-6.
Pico JL, Avila-Garavito A, Naccache P. Mucositis: Its Occurrence, Consequences, and Treatment in the Oncology Setting. Oncologist 1998;3:446-51.
Souba WW, Klimberg VS, Copeland EM 3 rd . Glutamine nutrition in the management of radiation enteritis. JPENJ Parenter Enteral Nutr 1990;14:106S-8.
Anderson PM, Schroeder G, Skubitz KM. Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 1998;83:1433-9.
Cockerham MB, Weinberger BB, Lerchie SB. Oral glutamine for the prevention of oral mucositis associated with high-dose paclitaxel and melphalan for autologous bone marrow transplantation. Ann Pharmacother 2000;34:300-3.

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[1] Dose AM. The symptom experience of mucositis, stomatitis, and xerostomia. Semin Oncol Nurs 1995;11:248-55.

[2] Zlotolow IM. General consideration in prevention and treatment of oral manifestation of cancer therapies. In: Berget AP, Weissman DE, editors. Principles and Practice of Supportive Oncology. Philadelphia, PA: Lippincott Raven; 1998. p. 237.

[3] Vissink A, Jansma J, Spijkervet FK, Burlage FR, Coppes RP. Oral sequele of head and neck radiotherapy. Crit Rev Oral Biol Med 2003;14:199-212.

[4] Lee DJ, Cosmatos D, Marcial VA, Fu KK, Rotman M, Cooper JS, et al. Results of an RTOG phaseIII trial (RTOG 85-27) comparing radiotherapy plus etanidazole with radiotherapy alone for locally advanced head and neck carcinomas. Int J Radiat Oncol Biol Phys 1995;32:567-76.

[5] Fu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL, et al. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: First report of RTOG 9003. Int J Radiat Oncol Biol Phys 2000;48:7-16.

[6] Bitran JD, Samuels B, Klein L, Hanauer S, Johnson L, Martinec J, et al. Tandem high-dose chemotherapy supported by hematopoietic progenitor cells yields prolonged survival in stage IV breast cancer. Bone Marrow Transplant 1996;17:157-62.

[7] Mead G M. Management of oral mucositis associated with cancer chemotherapy. Lancet 2002;359:815-6.

[8] Krebs H. Glutamine metabolism in the anima lbody. In: Mora J, Palacios R, editors. Glutamine: Metabolism, enzymology and regulation. NewYork: Academic Press; 1980. p. 319-25.

[9] Windmueller HG, Spaeth AE. Uptake and metabolism of plasma glutamine by the small intestine. J Biol Chem 1974;249:5070-9.

[10] Windmueller HG, Spaeth AE. Identification of ketone bodies and glutamine as the major respiratory fuels in vivo for post absorptive rat small intestine. J Biol Chem 1978;253:69-76.

[11] Baskerville A, Hambleton P, Benbough JE. Pathological features of glutaminase toxicity. Br J Exp Pathol 1980;61:132-8.

[12] Rouse K, Nwokedi E, Woodliff JE, Epstein J, Klimberg VS. Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism. Ann Surg 1995;221:420-6.

[13] Savarese DM, Savy G, Vahdat L, Wischmeyer PE, Corey B. Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treat Rev 2003;29:501-13.

[14] Klimberg VS, Kornbluth J, Cao Y, Dang A, Blossom S, Schaeffer RF. Glutamine suppresses PGE 2 synthesis and breast cancer growth. J Surg Res 1996;63:293-7.

[15] Shewchuk LD, Baracos VE, Field CJ. Dietary L-glutamine supplementation reduces the growth of the Morris Hepatoma7777 in exercise-trained and sedentary rats. J Nutr 1997;127:158-66.

[16] Ardawi MS, Newsholme EA. Glutamine metabolism in lymphocytes of the rat. Biochem J 1983;212:835-42.

[17] Klimberg VS, Souba WW, Dolson DJ, Salloum RM, Hautamaki RD, Plumley DA, et al. Prophylactic glutamine protects the intestinal mucosa from radiation injury. Cancer 1990;66:62-8.

[18] Huang EY, Leung SW, Wang CJ, Chen HC, Sun LM, Fang FM, et al. Oral glutamine to alleviate radiation-induced oral mucositis: A pilot randomized trial. Int J Radiat Oncol Biol Phys 2000;46:535-9.

[19] Silverman S Jr. Diagnosis and management of oral mucositis. J Support Oncol 2007;5(Suppl 1):13-21.

[20] Billings RJ, Proskin HM, Moss ME. Xerostomia and associated factors in a community-dwelling adult population. Community Dent Oral Epidemiol 1996;24:312-6.

[21] Pico JL, Avila-Garavito A, Naccache P. Mucositis: Its Occurrence, Consequences, and Treatment in the Oncology Setting. Oncologist 1998;3:446-51.

[22] Souba WW, Klimberg VS, Copeland EM 3 rd . Glutamine nutrition in the management of radiation enteritis. JPENJ Parenter Enteral Nutr 1990;14:106S-8.

[23] Anderson PM, Schroeder G, Skubitz KM. Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 1998;83:1433-9.

[24] Cockerham MB, Weinberger BB, Lerchie SB. Oral glutamine for the prevention of oral mucositis associated with high-dose paclitaxel and melphalan for autologous bone marrow transplantation. Ann Pharmacother 2000;34:300-3.

Role of oral glutamine in alleviation and prevention of radiation-induced oral mucositis: A prospective randomized study

Abstract

Abstract

Keywords

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