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Published in: BMC Cancer 1/2012

Open Access 01-12-2012 | Research article

Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

Authors: Erkan Topkan, Cem Parlak, Savas Topuk, Berrin Pehlivan

Published in: BMC Cancer | Issue 1/2012

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Abstract

Background

Glutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities.

Methods

The study included 104 patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS), local/regional progression-free survival (LRPFS), and overall survival (OS) were correlated with status of Gln supplementation.

Results

Oral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or late grade 4–5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of 24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0 months (p=0.11), respectively.

Conclusion

In our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial effect with respect to prevention of weight loss and unplanned treatment delays, and reduced the severity and incidence of acute- and late-RIE.
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Literature
1.
go back to reference Chapet O, Fraas BA, Ten Haken RK: Multiple fields may offer better esophagus sparing without increased probability of lung toxicity in optimized IMRT of lung tumors. Int J Radiat Oncol Biol Phys. 2006, 65: 255-265. 10.1016/j.ijrobp.2005.12.028.CrossRefPubMed Chapet O, Fraas BA, Ten Haken RK: Multiple fields may offer better esophagus sparing without increased probability of lung toxicity in optimized IMRT of lung tumors. Int J Radiat Oncol Biol Phys. 2006, 65: 255-265. 10.1016/j.ijrobp.2005.12.028.CrossRefPubMed
2.
go back to reference Citrin D, Cotrim AP, Hyodo F, Baum BJ, Krishna MC, Mitchell JB: Radioprotectors and mitigators of radiation-induced normal tissue injury. Oncologist. 2010, 15 (4): 360-71. 10.1634/theoncologist.2009-S104.CrossRefPubMedPubMedCentral Citrin D, Cotrim AP, Hyodo F, Baum BJ, Krishna MC, Mitchell JB: Radioprotectors and mitigators of radiation-induced normal tissue injury. Oncologist. 2010, 15 (4): 360-71. 10.1634/theoncologist.2009-S104.CrossRefPubMedPubMedCentral
3.
go back to reference Savarese DM, Savy G, Vahdat L, Wischmeyer PE, Corey B: Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treat Rev. 2003, 29 (6): 501-513. 10.1016/S0305-7372(03)00133-6.CrossRefPubMed Savarese DM, Savy G, Vahdat L, Wischmeyer PE, Corey B: Prevention of chemotherapy and radiation toxicity with glutamine. Cancer Treat Rev. 2003, 29 (6): 501-513. 10.1016/S0305-7372(03)00133-6.CrossRefPubMed
4.
go back to reference Kuhn KS, Muscaritoli M, Wischmeyer P, Stehle P: Glutamine as indispensable nutrient in oncology: experimental and clinical evidence. Eur J Nutr. 2010, 49 (4): 197-210. 10.1007/s00394-009-0082-2.CrossRefPubMed Kuhn KS, Muscaritoli M, Wischmeyer P, Stehle P: Glutamine as indispensable nutrient in oncology: experimental and clinical evidence. Eur J Nutr. 2010, 49 (4): 197-210. 10.1007/s00394-009-0082-2.CrossRefPubMed
5.
go back to reference Kapadia C, Muhlbacher F, Smith R: Alterations in glutamine metabolism in response to operative stress and food deprivation. Surg Forum. 1982, 33: 19-21. Kapadia C, Muhlbacher F, Smith R: Alterations in glutamine metabolism in response to operative stress and food deprivation. Surg Forum. 1982, 33: 19-21.
6.
go back to reference Rouse K, Nwokedi E, Woodliff JE, Epstein J, Klimberg VS: Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism. Ann Surg. 1995, 221 (4): 420-426. 10.1097/00000658-199504000-00014.CrossRefPubMedPubMedCentral Rouse K, Nwokedi E, Woodliff JE, Epstein J, Klimberg VS: Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism. Ann Surg. 1995, 221 (4): 420-426. 10.1097/00000658-199504000-00014.CrossRefPubMedPubMedCentral
7.
go back to reference Klimberg VS, Nwokedi B: LF H: Does glutamine facilitate chemotherapy while reducing its toxicity?. Surg Forum. 1991, 42: 16-18. Klimberg VS, Nwokedi B: LF H: Does glutamine facilitate chemotherapy while reducing its toxicity?. Surg Forum. 1991, 42: 16-18.
8.
go back to reference Carretero J, Obrador E, Pellicer JA, Pascual A, Estrela JM: Mitochondrial glutathione depletion by glutamine in growing tumor cells. Free Radic Biol Med. 2000, 29 (9): 913-923. 10.1016/S0891-5849(00)00392-0.CrossRefPubMed Carretero J, Obrador E, Pellicer JA, Pascual A, Estrela JM: Mitochondrial glutathione depletion by glutamine in growing tumor cells. Free Radic Biol Med. 2000, 29 (9): 913-923. 10.1016/S0891-5849(00)00392-0.CrossRefPubMed
9.
go back to reference Algara M, Rodriguez N, Vinals P, Lacruz M, Foro P, Reig A, Quera J, Lozano J, Fernandez-Velilla E, Membrive I, et al: Prevention of radiochemotherapy-induced esophagitis with glutamine: results of a pilot study. Int J Radiat Oncol Biol Phys. 2007, 69 (2): 342-349. 10.1016/j.ijrobp.2007.03.041.CrossRefPubMed Algara M, Rodriguez N, Vinals P, Lacruz M, Foro P, Reig A, Quera J, Lozano J, Fernandez-Velilla E, Membrive I, et al: Prevention of radiochemotherapy-induced esophagitis with glutamine: results of a pilot study. Int J Radiat Oncol Biol Phys. 2007, 69 (2): 342-349. 10.1016/j.ijrobp.2007.03.041.CrossRefPubMed
10.
go back to reference Topkan E, Yavuz MN, Onal C, Yavuz AA: Prevention of acute radiation-induced esophagitis with glutamine in non-small cell lung cancer patients treated with radiotherapy: evaluation of clinical and dosimetric parameters. Lung Cancer. 2009, 63 (3): 393-399. 10.1016/j.lungcan.2008.06.015.CrossRefPubMed Topkan E, Yavuz MN, Onal C, Yavuz AA: Prevention of acute radiation-induced esophagitis with glutamine in non-small cell lung cancer patients treated with radiotherapy: evaluation of clinical and dosimetric parameters. Lung Cancer. 2009, 63 (3): 393-399. 10.1016/j.lungcan.2008.06.015.CrossRefPubMed
11.
go back to reference Bourhis J, Blanchard P, Maillard E, Brizel DM, Movsas B, Buentzel J, Langendijk JA, Komaki R, Swan Leong S, Levendag P, et al: Effect of amifostine on survival among patients treated with radiotherapy: a meta-analysis of individual patient data. J Clin Oncol. 2011, 29 (18): 2590-2597. 10.1200/JCO.2010.33.1454.CrossRefPubMed Bourhis J, Blanchard P, Maillard E, Brizel DM, Movsas B, Buentzel J, Langendijk JA, Komaki R, Swan Leong S, Levendag P, et al: Effect of amifostine on survival among patients treated with radiotherapy: a meta-analysis of individual patient data. J Clin Oncol. 2011, 29 (18): 2590-2597. 10.1200/JCO.2010.33.1454.CrossRefPubMed
12.
go back to reference Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, Zwahlen M, Clarke M, Weingart O, Kluge S, et al: Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials. Lancet. 2009, 373 (9674): 1532-1542. 10.1016/S0140-6736(09)60502-X.CrossRefPubMed Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, Zwahlen M, Clarke M, Weingart O, Kluge S, et al: Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials. Lancet. 2009, 373 (9674): 1532-1542. 10.1016/S0140-6736(09)60502-X.CrossRefPubMed
13.
go back to reference Eagle H: Nutritional needs of mammalian cells in tissue culture. Science. 1935, 122: 501-CrossRef Eagle H: Nutritional needs of mammalian cells in tissue culture. Science. 1935, 122: 501-CrossRef
14.
go back to reference Collins CL, Wasa M, Souba WW, Abcouwer SF: Determinants of glutamine dependence and utilization by normal and tumor-derived breast cell lines. J Cell Physiol. 1998, 176: 166-178. 10.1002/(SICI)1097-4652(199807)176:1<166::AID-JCP18>3.0.CO;2-5.CrossRefPubMed Collins CL, Wasa M, Souba WW, Abcouwer SF: Determinants of glutamine dependence and utilization by normal and tumor-derived breast cell lines. J Cell Physiol. 1998, 176: 166-178. 10.1002/(SICI)1097-4652(199807)176:1<166::AID-JCP18>3.0.CO;2-5.CrossRefPubMed
15.
go back to reference Sauer LA, Dauchy RT: Ketone body, glucose, lactic acid, and amino acid utilization by tumors in vivo in fasted rats. Cancer Res. 1983, 43: 3497-3503.PubMed Sauer LA, Dauchy RT: Ketone body, glucose, lactic acid, and amino acid utilization by tumors in vivo in fasted rats. Cancer Res. 1983, 43: 3497-3503.PubMed
16.
go back to reference Choi K, Lee SS, Oh SJ, Lim SY, Lim SY, Jeon WK, Oh TY, Kim JW: The effect of oral glutamine on 5-fluorouracil/ leucovorin-induced mucositis/stomatitis assessed by intestinal permeability test. Clin Nutr. 2007, 26: 57-62. 10.1016/j.clnu.2006.07.003.CrossRefPubMed Choi K, Lee SS, Oh SJ, Lim SY, Lim SY, Jeon WK, Oh TY, Kim JW: The effect of oral glutamine on 5-fluorouracil/ leucovorin-induced mucositis/stomatitis assessed by intestinal permeability test. Clin Nutr. 2007, 26: 57-62. 10.1016/j.clnu.2006.07.003.CrossRefPubMed
17.
go back to reference Wang WS, Lin JK, Lin TC, Chen WS, Jiang JK, Wang HS, Chiou TJ, Liu JH, Yen CC, Chen PM: Oral glutamine is effective for preventing oxaliplatin-induced neuropathy in colorectal cancer patients. Oncologist. 2007, 12: 312-319. 10.1634/theoncologist.12-3-312.CrossRefPubMed Wang WS, Lin JK, Lin TC, Chen WS, Jiang JK, Wang HS, Chiou TJ, Liu JH, Yen CC, Chen PM: Oral glutamine is effective for preventing oxaliplatin-induced neuropathy in colorectal cancer patients. Oncologist. 2007, 12: 312-319. 10.1634/theoncologist.12-3-312.CrossRefPubMed
18.
go back to reference Monteforte MJ, Turkelson CM: Bariatric surgery for morbid obesity. Obes Surg. 2000, 10 (5): 391-401. 10.1381/096089200321594246.CrossRefPubMed Monteforte MJ, Turkelson CM: Bariatric surgery for morbid obesity. Obes Surg. 2000, 10 (5): 391-401. 10.1381/096089200321594246.CrossRefPubMed
19.
go back to reference Cox JD, Stez J, Pajak TF: Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995, 31: 1341-1346. 10.1016/0360-3016(95)00060-C.CrossRefPubMed Cox JD, Stez J, Pajak TF: Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995, 31: 1341-1346. 10.1016/0360-3016(95)00060-C.CrossRefPubMed
20.
go back to reference Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, Pruim J, Price P: Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999, 35 (13): 1773-1782. 10.1016/S0959-8049(99)00229-4.CrossRefPubMed Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, Pruim J, Price P: Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999, 35 (13): 1773-1782. 10.1016/S0959-8049(99)00229-4.CrossRefPubMed
21.
go back to reference Bartlett DL, Charland S, Torosian MH: Effect of glutamine on tumor and host growth. Ann Surg Oncol. 1995, 2 (1): 71-76. 10.1007/BF02303705.CrossRefPubMed Bartlett DL, Charland S, Torosian MH: Effect of glutamine on tumor and host growth. Ann Surg Oncol. 1995, 2 (1): 71-76. 10.1007/BF02303705.CrossRefPubMed
22.
go back to reference Klimberg VS, Souba WW, Salloum RM, Plumley DA, Cohen FS, Dolson DJ, Bland KI, Copeland EM: Glutamine-enriched diets support muscle glutamine metabolism without stimulating tumor growth. J Surg Res. 1990, 48 (4): 319-323. 10.1016/0022-4804(90)90066-B.CrossRefPubMed Klimberg VS, Souba WW, Salloum RM, Plumley DA, Cohen FS, Dolson DJ, Bland KI, Copeland EM: Glutamine-enriched diets support muscle glutamine metabolism without stimulating tumor growth. J Surg Res. 1990, 48 (4): 319-323. 10.1016/0022-4804(90)90066-B.CrossRefPubMed
23.
go back to reference van der Hulst RR, van Kreel BK, von Meyenfeldt MF, Brummer RJ, Arends JW, Deutz NE, Soeters PB: Glutamine and the preservation of gut integrity. Lancet. 1993, 341 (8857): 1363-1365. 10.1016/0140-6736(93)90939-E.CrossRefPubMed van der Hulst RR, van Kreel BK, von Meyenfeldt MF, Brummer RJ, Arends JW, Deutz NE, Soeters PB: Glutamine and the preservation of gut integrity. Lancet. 1993, 341 (8857): 1363-1365. 10.1016/0140-6736(93)90939-E.CrossRefPubMed
24.
go back to reference Shewchuk LD, Baracos VE, Field CJ: Dietary L-glutamine supplementation reduces the growth of the Morris Hepatoma 7777 in exercise-trained and sedentary rats. J Nutr. 1997, 127 (1): 158-166.PubMed Shewchuk LD, Baracos VE, Field CJ: Dietary L-glutamine supplementation reduces the growth of the Morris Hepatoma 7777 in exercise-trained and sedentary rats. J Nutr. 1997, 127 (1): 158-166.PubMed
25.
go back to reference Klimberg VS, Souba WW, Dolson DJ, Salloum RM, Hautamaki RD, Plumley DA, Mendenhall WM, Bova FJ, Khan SR, Hackett RL, et al: Prophylactic glutamine protects the intestinal mucosa from radiation injury. Cancer. 1990, 66 (1): 62-68. 10.1002/1097-0142(19900701)66:1<62::AID-CNCR2820660113>3.0.CO;2-E.CrossRefPubMed Klimberg VS, Souba WW, Dolson DJ, Salloum RM, Hautamaki RD, Plumley DA, Mendenhall WM, Bova FJ, Khan SR, Hackett RL, et al: Prophylactic glutamine protects the intestinal mucosa from radiation injury. Cancer. 1990, 66 (1): 62-68. 10.1002/1097-0142(19900701)66:1<62::AID-CNCR2820660113>3.0.CO;2-E.CrossRefPubMed
26.
go back to reference Klimberg V: How glutamine protects the gut during irradiation. J Crit Care Nutr. 1996, 3: 21-25. Klimberg V: How glutamine protects the gut during irradiation. J Crit Care Nutr. 1996, 3: 21-25.
27.
go back to reference Jensen JC, Schaefer R, Nwokedi E, Bevans DW, Baker ML, Pappas AA, Westbrook KC, Klimberg VS: Prevention of chronic radiation enteropathy by dietary glutamine. Ann Surg Oncol. 1994, 1 (2): 157-163. 10.1007/BF02303560.CrossRefPubMed Jensen JC, Schaefer R, Nwokedi E, Bevans DW, Baker ML, Pappas AA, Westbrook KC, Klimberg VS: Prevention of chronic radiation enteropathy by dietary glutamine. Ann Surg Oncol. 1994, 1 (2): 157-163. 10.1007/BF02303560.CrossRefPubMed
28.
go back to reference Souba WW, Klimberg VS, Hautamaki RD, Mendenhall WH, Bova FC, Howard RJ, Bland KI, Copeland EM: Oral glutamine reduces bacterial translocation following abdominal radiation. J Surg Res. 1990, 48 (1): 1-5. 10.1016/0022-4804(90)90136-P.CrossRefPubMed Souba WW, Klimberg VS, Hautamaki RD, Mendenhall WH, Bova FC, Howard RJ, Bland KI, Copeland EM: Oral glutamine reduces bacterial translocation following abdominal radiation. J Surg Res. 1990, 48 (1): 1-5. 10.1016/0022-4804(90)90136-P.CrossRefPubMed
29.
go back to reference Salman B, Oguz M, Akmansu M, Bebitoglu I, Akca G, Sultan N, Emre U, Kerem M, Yilmaz U: Effect of timing of glutamine-enriched enteral nutrition on intestinal damage caused by irradiation. Adv Ther. 2007, 24 (3): 648-661. 10.1007/BF02848790.CrossRefPubMed Salman B, Oguz M, Akmansu M, Bebitoglu I, Akca G, Sultan N, Emre U, Kerem M, Yilmaz U: Effect of timing of glutamine-enriched enteral nutrition on intestinal damage caused by irradiation. Adv Ther. 2007, 24 (3): 648-661. 10.1007/BF02848790.CrossRefPubMed
30.
go back to reference Huang EY, Leung SW, Wang CJ, Chen HC, Sun LM, Fang FM, Yeh SA, Hsu HC, Hsiung CY: Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial. Int J Radiat Oncol Biol Phys. 2000, 46 (3): 535-539. 10.1016/S0360-3016(99)00402-2.CrossRefPubMed Huang EY, Leung SW, Wang CJ, Chen HC, Sun LM, Fang FM, Yeh SA, Hsu HC, Hsiung CY: Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial. Int J Radiat Oncol Biol Phys. 2000, 46 (3): 535-539. 10.1016/S0360-3016(99)00402-2.CrossRefPubMed
31.
go back to reference Yoshida S, Matsui M, Shirouzu Y, Fujita H, Yamana H, Shirouzu K: Effects of glutamine supplements and radiochemotherapy on systemic immune and gut barrier function in patients with advanced esophageal cancer. Ann Surg. 1998, 227 (4): 485-491. 10.1097/00000658-199804000-00006.CrossRefPubMedPubMedCentral Yoshida S, Matsui M, Shirouzu Y, Fujita H, Yamana H, Shirouzu K: Effects of glutamine supplements and radiochemotherapy on systemic immune and gut barrier function in patients with advanced esophageal cancer. Ann Surg. 1998, 227 (4): 485-491. 10.1097/00000658-199804000-00006.CrossRefPubMedPubMedCentral
32.
go back to reference Cerchietti LC, Navigante AH, Lutteral MA, Castro MA, Kirchuk R, Bonomi M, Cabalar ME, Roth B, Negretti G, Sheinker B, et al: Double-blinded, placebo-controlled trial on intravenous L-alanyl-L-glutamine in the incidence of oral mucositis following chemoradiotherapy in patients with head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2006, 65 (5): 1330-1337. 10.1016/j.ijrobp.2006.03.042.CrossRefPubMed Cerchietti LC, Navigante AH, Lutteral MA, Castro MA, Kirchuk R, Bonomi M, Cabalar ME, Roth B, Negretti G, Sheinker B, et al: Double-blinded, placebo-controlled trial on intravenous L-alanyl-L-glutamine in the incidence of oral mucositis following chemoradiotherapy in patients with head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2006, 65 (5): 1330-1337. 10.1016/j.ijrobp.2006.03.042.CrossRefPubMed
33.
go back to reference Anderson PM, Ramsay NK, Shu XO, Rydholm N, Rogosheske J, Nicklow R, Weisdorf DJ, Skubitz KM: Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. Bone Marrow Transplant. 1998, 22 (4): 339-344. 10.1038/sj.bmt.1701317.CrossRefPubMed Anderson PM, Ramsay NK, Shu XO, Rydholm N, Rogosheske J, Nicklow R, Weisdorf DJ, Skubitz KM: Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. Bone Marrow Transplant. 1998, 22 (4): 339-344. 10.1038/sj.bmt.1701317.CrossRefPubMed
34.
go back to reference Schloerb PR, Skikne BS: Oral and parenteral glutamine in bone marrow transplantation: a randomized, double-blind study. JPEN J Parenter Enteral Nutr. 1999, 23 (3): 117-122. 10.1177/0148607199023003117.CrossRefPubMed Schloerb PR, Skikne BS: Oral and parenteral glutamine in bone marrow transplantation: a randomized, double-blind study. JPEN J Parenter Enteral Nutr. 1999, 23 (3): 117-122. 10.1177/0148607199023003117.CrossRefPubMed
35.
go back to reference Vahdat L, Papadopoulos K, Lange D, Leuin S, Kaufman E, Donovan D, Frederick D, Bagiella E, Tiersten A, Nichols G, et al: Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res. 2001, 7 (5): 1192-1197.PubMed Vahdat L, Papadopoulos K, Lange D, Leuin S, Kaufman E, Donovan D, Frederick D, Bagiella E, Tiersten A, Nichols G, et al: Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res. 2001, 7 (5): 1192-1197.PubMed
36.
go back to reference Li Y, Yu Z, Liu F, Tan L, Wu B, Li J: Oral glutamine ameliorates chemotherapy-induced changes of intestinal permeability and does not interfere with the antitumor effect of chemotherapy in patients with breast cancer: a prospective randomized trial. Tumori. 2006, 92 (5): 396-401.PubMed Li Y, Yu Z, Liu F, Tan L, Wu B, Li J: Oral glutamine ameliorates chemotherapy-induced changes of intestinal permeability and does not interfere with the antitumor effect of chemotherapy in patients with breast cancer: a prospective randomized trial. Tumori. 2006, 92 (5): 396-401.PubMed
37.
go back to reference Bode BP, Kaminski DL, Souba WW, Li AP: Glutamine transport in isolated human hepatocytes and transformed liver cells. Hepatology. 1995, 21 (2): 511-520.PubMed Bode BP, Kaminski DL, Souba WW, Li AP: Glutamine transport in isolated human hepatocytes and transformed liver cells. Hepatology. 1995, 21 (2): 511-520.PubMed
39.
go back to reference Knox WE, Horowitz ML, Friedell GH: The proportionality of glutaminase content to growth rate and morphology of rat neoplasms. Cancer Res. 1969, 29 (3): 669-680.PubMed Knox WE, Horowitz ML, Friedell GH: The proportionality of glutaminase content to growth rate and morphology of rat neoplasms. Cancer Res. 1969, 29 (3): 669-680.PubMed
40.
go back to reference Obrador E, Carretero J, Esteve JM, Pellicer JA, Pascual A, Petschen I, Estrela JM: Glutamine potentiates TNF-alpha-induced tumor cytotoxicity. Free Radic Biol Med. 2001, 31 (5): 642-650. 10.1016/S0891-5849(01)00622-0.CrossRefPubMed Obrador E, Carretero J, Esteve JM, Pellicer JA, Pascual A, Petschen I, Estrela JM: Glutamine potentiates TNF-alpha-induced tumor cytotoxicity. Free Radic Biol Med. 2001, 31 (5): 642-650. 10.1016/S0891-5849(01)00622-0.CrossRefPubMed
41.
go back to reference Fahr MJ, Kornbluth J, Blossom S, Schaeffer R, Klimberg VS, Harry M: Vars Research Award. Glutamine enhances immunoregulation of tumor growth. JPEN J Parenter Enteral Nutr. 1994, 18 (6): 471-476. 10.1177/0148607194018006471.CrossRefPubMed Fahr MJ, Kornbluth J, Blossom S, Schaeffer R, Klimberg VS, Harry M: Vars Research Award. Glutamine enhances immunoregulation of tumor growth. JPEN J Parenter Enteral Nutr. 1994, 18 (6): 471-476. 10.1177/0148607194018006471.CrossRefPubMed
42.
go back to reference El-Malt M, Ceelen W, Boterberg T, Claeys G, de Hemptinne B, de Neve W, Pattyn P: Does the addition of glutamine to total parenteral nutrition have beneficial effect on the healing of colon anastomosis and bacterial translocation after preoperative radiotherapy?. Am J Clin Oncol. 2003, 26 (3): e54-59.PubMed El-Malt M, Ceelen W, Boterberg T, Claeys G, de Hemptinne B, de Neve W, Pattyn P: Does the addition of glutamine to total parenteral nutrition have beneficial effect on the healing of colon anastomosis and bacterial translocation after preoperative radiotherapy?. Am J Clin Oncol. 2003, 26 (3): e54-59.PubMed
43.
go back to reference Kozelsky TF, Meyers GE, Sloan JA, Shanahan TG, Dick SJ, Moore RL, Engeler GP, Frank AR, McKone TK, Urias RE, et al: Phase III double-blind study of glutamine versus placebo for the prevention of acute diarrhea in patients receiving pelvic radiation therapy. J Clin Oncol. 2003, 21 (9): 1669-1674. 10.1200/JCO.2003.05.060.CrossRefPubMed Kozelsky TF, Meyers GE, Sloan JA, Shanahan TG, Dick SJ, Moore RL, Engeler GP, Frank AR, McKone TK, Urias RE, et al: Phase III double-blind study of glutamine versus placebo for the prevention of acute diarrhea in patients receiving pelvic radiation therapy. J Clin Oncol. 2003, 21 (9): 1669-1674. 10.1200/JCO.2003.05.060.CrossRefPubMed
44.
go back to reference Yamamoto N, Nakagawa K, Nishimura Y, Tsujino K, Satouchi M, Kudo S, Hida T, Kawahara M, Takeda K, Katakami N, et al: Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol. 2010, 28 (23): 3739-3745. 10.1200/JCO.2009.24.5050.CrossRefPubMed Yamamoto N, Nakagawa K, Nishimura Y, Tsujino K, Satouchi M, Kudo S, Hida T, Kawahara M, Takeda K, Katakami N, et al: Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol. 2010, 28 (23): 3739-3745. 10.1200/JCO.2009.24.5050.CrossRefPubMed
45.
go back to reference Segawa Y, Kiura K, Takigawa N, Kamei H, Harita S, Hiraki S, Watanabe Y, Sugimoto K, Shibayama T, Yonei T, et al: Phase III trial comparing docetaxel and cisplatin combination chemotherapy with mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiotherapy in locally advanced non-small-cell lung cancer: OLCSG 0007. J Clin Oncol. 2010, 28 (20): 3299-3306. 10.1200/JCO.2009.24.7577.CrossRefPubMed Segawa Y, Kiura K, Takigawa N, Kamei H, Harita S, Hiraki S, Watanabe Y, Sugimoto K, Shibayama T, Yonei T, et al: Phase III trial comparing docetaxel and cisplatin combination chemotherapy with mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiotherapy in locally advanced non-small-cell lung cancer: OLCSG 0007. J Clin Oncol. 2010, 28 (20): 3299-3306. 10.1200/JCO.2009.24.7577.CrossRefPubMed
46.
go back to reference Blumenschein GR, Paulus R, Curran WJ, Robert F, Fossella F, Werner-Wasik M, Herbst RS, Doescher PO, Choy H, Komaki R: Phase II study of cetuximab in combination with chemoradiation in patients with stage IIIA/B non-small-cell lung cancer: RTOG 0324. J Clin Oncol. 2011, 29 (17): 2312-2318. 10.1200/JCO.2010.31.7875.CrossRefPubMedPubMedCentral Blumenschein GR, Paulus R, Curran WJ, Robert F, Fossella F, Werner-Wasik M, Herbst RS, Doescher PO, Choy H, Komaki R: Phase II study of cetuximab in combination with chemoradiation in patients with stage IIIA/B non-small-cell lung cancer: RTOG 0324. J Clin Oncol. 2011, 29 (17): 2312-2318. 10.1200/JCO.2010.31.7875.CrossRefPubMedPubMedCentral
47.
go back to reference Curran WJ, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, et al: Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011, 103 (19): 1452-1460. 10.1093/jnci/djr325.CrossRefPubMedPubMedCentral Curran WJ, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, et al: Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011, 103 (19): 1452-1460. 10.1093/jnci/djr325.CrossRefPubMedPubMedCentral
48.
go back to reference Brade A, Bezjak A, MacRae R, Laurie S, Sun A, Cho J, Leighl N, Pearson S, Southwood B, Wang L, et al: Phase I trial of radiation with concurrent and consolidation pemetrexed and cisplatin in patients with unresectable stage IIIA/B non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2011, 79 (5): 1395-1401. 10.1016/j.ijrobp.2010.01.014.CrossRefPubMed Brade A, Bezjak A, MacRae R, Laurie S, Sun A, Cho J, Leighl N, Pearson S, Southwood B, Wang L, et al: Phase I trial of radiation with concurrent and consolidation pemetrexed and cisplatin in patients with unresectable stage IIIA/B non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2011, 79 (5): 1395-1401. 10.1016/j.ijrobp.2010.01.014.CrossRefPubMed
49.
go back to reference Govindan R, Bogart J, Stinchcombe T, Wang X, Hodgson L, Kratzke R, Garst J, Brotherton T, Vokes EE: Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer: Cancer and Leukemia Group B trial 30407. J Clin Oncol. 2011, 29 (23): 3120-3125. 10.1200/JCO.2010.33.4979.CrossRefPubMedPubMedCentral Govindan R, Bogart J, Stinchcombe T, Wang X, Hodgson L, Kratzke R, Garst J, Brotherton T, Vokes EE: Randomized phase II study of pemetrexed, carboplatin, and thoracic radiation with or without cetuximab in patients with locally advanced unresectable non-small-cell lung cancer: Cancer and Leukemia Group B trial 30407. J Clin Oncol. 2011, 29 (23): 3120-3125. 10.1200/JCO.2010.33.4979.CrossRefPubMedPubMedCentral
50.
go back to reference El Sharouni SY, Kal HB, Battermann JJ: Accelerated regrowth of non-small-cell lung tumours after induction chemotherapy. Br J Cancer. 2003, 89 (12): 2184-2189. 10.1038/sj.bjc.6601418.CrossRefPubMedPubMedCentral El Sharouni SY, Kal HB, Battermann JJ: Accelerated regrowth of non-small-cell lung tumours after induction chemotherapy. Br J Cancer. 2003, 89 (12): 2184-2189. 10.1038/sj.bjc.6601418.CrossRefPubMedPubMedCentral
51.
go back to reference Koukourakis M, Hlouverakis G, Kosma L, Skarlatos J, Damilakis J, Giatromanolaki A, Yannakakis D: The impact of overall treatment time on the results of radiotherapy for nonsmall cell lung carcinoma. Int J Radiat Oncol Biol Phys. 1996, 34 (2): 315-322. 10.1016/0360-3016(95)02102-7.CrossRefPubMed Koukourakis M, Hlouverakis G, Kosma L, Skarlatos J, Damilakis J, Giatromanolaki A, Yannakakis D: The impact of overall treatment time on the results of radiotherapy for nonsmall cell lung carcinoma. Int J Radiat Oncol Biol Phys. 1996, 34 (2): 315-322. 10.1016/0360-3016(95)02102-7.CrossRefPubMed
Metadata
Title
Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer
Authors
Erkan Topkan
Cem Parlak
Savas Topuk
Berrin Pehlivan
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2012
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-12-502

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