HomeVolumesJMA, vol. XIX, iss. 1, 2016MUCOSITIS PATHOLOGY IN CHEMOTHERAPY INDUCED DIGESTIVE TOXICITY

MUCOSITIS PATHOLOGY IN CHEMOTHERAPY INDUCED DIGESTIVE TOXICITY


MUCOSITIS PATHOLOGY IN CHEMOTHERAPY INDUCED DIGESTIVE TOXICITY

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Article_Title: MUCOSITIS PATHOLOGY IN CHEMOTHERAPY INDUCED DIGESTIVE TOXICITY
Authors: Alciona Sasu*1,2, Mircea Onel1,2, Cornel Balta3, Cristina Ghib-Para1, Eftimie Miutescu4, Coralia Cotoraci1,2
Affiliation: 1 “Vasile Goldiş” Western University, Arad, Faculty of Medicine, Hematology Department
2 Emergency Clinical County Hospital of Arad, Hematology Clinic
3 “Vasile Goldiş” Western University, Arad, Institute of Life Sciences
4 “Vasile Goldiş” Western University, Arad, Faculty of Medicine, Gastroenterology Department
Abstract: Cytostatic chemotherapy can produce toxicity in the digestive tract at standard doses, in regimens given for various malignancies. Mucositis or gastrointestinal mucosal chemotherapy toxicity decreases the oncology patient’s quality of life and often leads to chemotherapy dose-reduction or even its discontinuation. This paper has two objectives: to emphasize a synthesis of data from the literature on the manifestation and pathogenesis of mucositis and, secondly, to present a study on the clinical mucositis on a group of patients receiving chemotherapy. The results showed that 61% of applications of chemotherapy are accompanied by digestive toxicity and each patient has at least one episode of nausea during cytostatic therapy. Understanding the mechanisms of mucositis allow the clinician to have a complex approach to the oncological patient receiving chemotherapy and find adjuvant substances that prevent or reduce this type of toxicity.
Keywords: mucositis, chemotherapy, gastrointestinal tract, intestinal toxicity, histopathology
References: • Al-Azri AR, RJ Gibson, DMK Keefe, RM Logan, Matrix metalloproteinases: do they play a role in mucosal pathology of the oral cavity?, Oral Diseases doi:10.1111/odi.12023, 2012
• Al-Dasooqi N, Bowen J, Gibson R, Stringer A, Logan R, Keefe D, Irinotecan-induced mucositis encompasses changes in intestinal and colonic cell kinetics and this is associated with altered extracellular matrix component expression, Journal of Gastroenterology and Hepatology, 25:A2-A2, October 2010
• Al-Dasooqi N, Bowen JM, Gibson RJ, Logan RM, Stringer AM, Keefe DM, Irinotecan-induced alterations in intestinal cell kinetics and extracellular matrix component expression in the dark agouti rat, Int. J. Exp. Path., doi: 10.1111/j.1365-2613.2011.00771.x, 2011
• Al-Dasooqi N, Gibson RJ, Bowen JM, Logan RM, Stringer AM, Keefe DM, Matrix metalloproteinases are possible mediators for the development of alimentary tract mucositis in the dark agouti rat, Experimental Biology and Medicine; 235: 1244–1256. DOI: 10.1258/ebm.2010.010082, 2010
• Beijnen J, Drug interactions in oncology, The Lancet Oncology, Volume 5, Issue 8, Pages 489–496, 2004
• Boige V, Mendiboure J, Pignon JP, et al., Pharmacogenetic Assessment of Toxicity and Outcome in Patients With Metastatic Colorectal Cancer Treated With LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05, JCO vol. 28 no. 15 2556-2564, 2010
• Bommu P, Nanjan CMJ, Joghee NM, Nataraj SM, Bhojraj S, Phyllanthus maderaspatensis, a dietary supplement for the amelioration of adriamycin-induced toxicity and oxidative stress in mice, J Nat Med. 2008 Apr;62(2):149-54. doi: 10.1007/s11418-007-0204-1. Epub 2007 Oct 24.
• Boussios S, Pentheroudakis G, Katsanos K, Pavlidisa N, Systemic treatment-induced gastrointestinal toxicity: incidence, clinical presentation and management, Ann Gastroenterol.; 25(2): 106–118. PMCID: PMC3959393, 2012
• Bowen JM, Gibson RJ, Keefe DM, Cummins AG, Cytotoxic chemotherapy upregulates pro‐apoptotic Bax and Bak in the small intestine of rats and humans, Pathology, Volume 37, Issue 1, 2005
• Bressana V, Stevaninb S, Bianchic M, Aleoc G, Bagnascoc A, Sassoc L, Cancer Treatment Reviews, Volume 45, Pages 105–119, Systematic or Meta-analysis Studies, The effects of swallowing disorders, dysgeusia, oral mucositis and xerostomia on nutritional status, oral intake and weight loss in head and neck cancer patients: A systematic review, , doi:10.1016/j.ctrv.2016.03.006, April 2016
• Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010) U.S.DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute, http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf, accessed 5 May 2016
• Cunningham D, Morgan RJ, Mills PR, Nelson LM, Toner PG, Soukop M, McArdle CS, Russell RI, Functional and structural changes of the human proximal small intestine after cytotoxic therapy, J Clin Pathol 38(3): 265-70, 1985
• Das J, Ghosh J, Manna P, Sil PC, Taurine protects rat testes against doxorubicin-induced oxidative stress as well as p53, Fas and caspase 12-mediated apoptosis, Amino Acids 42:1839–1855; DOI 10.1007/s00726-011-0904-4, 2012
• Di Palma M, Prise en charge des mucites chez les patients traitées pour un cancer du sein Groupe de travail : M. Di Palma, J.-P. Durand, L. Juhel, F. Scotte´ , C. Villanueva, Oncologie ISSN 1292-3818, 2009
• Duncan M, Grant G, Oral and intestinal mucositis — causes and possible treatments, Alimentary Pharmacologics and Therapeutics, Volume 18, Issue 9, Pages 853–874, DOI: 10.1046/j.1365-2036.2003.01784.x, Nov 2003
• Engelking C, Rutledge DN, Ippoliti C, Neumann J, Hogan CM. Cancer related diarrhea: a neglected cause of cancer-related symptom distress. Oncol Nurs Forum; 25:859-860, 1998
• Fijlstra M, Rings EHHM, van Dijk TH, Plösch T, Verkade HJ, Tissing WJE, Continuous enteral administration can overcome the limited capacity to absorb glucose in rats with methotrexate-induced gastrointestinal mucositis, Supportive Care in Cancer, Volume 21, Issue 3, pp 863–871, March 2013
• Freter CE, Perry MC, Systemic therapy. In Abelofff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG (eds) Abeloff’s Clinical Oncology. Fourth Edition, Churchill Livingstone Elsevier, Phildelphia PA 2008: 449- 483, 2008
• Gibson RJ, Bowen JM, Keefe DMK, Technological advances in mucositis research: New insights and new issues, Cancer Treatment Reviews; 34, 476– 482, 2008
• Gibson RJ, Cummins AG, Bowen JM, Logan RM, Healey T, Keefe DM, Apoptosis occurs early in the basal layer of the oral mucosa following cancer chemotherapy, Asia–Pacific Journal of Clinical Oncology; 2: 39–49, 2006
• Gibson RJ, Bowen JM, Inglis MR, Cummins AG, Keefe DMK, Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer, DOI: 10.1046/j.1440-1746.2003.03136.x, JGHF, Volume 18, Issue 9, Pages 1095–1100, September 2003
• Gibson RJ, Keefe DMK, Thompson FM, Clarke JM, Goland GJ, Cummins AG, Effect of Interleukin-11 on Ameliorating Intestinal Damage After Methotrexate Treatment of Breast Cancer in Rats, Digestive Diseases and Sciences, Volume 47, Issue 12, pp 2751–2757, Dec 2002
• Herbers AH, de Haan AF, van der Velden WJ, Donnelly JP, Blijlevens NM, Mucositis not neutropenia determines bacteremia among hematopoietic stem cell transplant recipients, Transpl Infect Dis. 2014 Apr;16(2):279-85. doi: 10.1111/tid.12195. Epub 2014 Mar 13
• Hoffman R, Benz EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J. Hematology, Basic Principles and Practice. 6th Edition, Churchill Livingstone Title
ISBN: 978-1-4377-2928-3, 2384 pages, 2013
• Hurria A, Togawa K, Mohile SG, Owusu C, Klepin D, Gross C, Lichtman SM, Katheria V, Klapper S, Tew WP. Predicting Chemotherapy Toxicity in Older Adults with Cancer: A Prospective 500 Patient Multicenter Study [Abstract 9001]. American Society of Clinical Oncology, 2010
• Ijiri K and C. S. Potten, Response of intestinal cells of differing topographical and hierarchical status to ten cytotoxic drugs and five sources of radiation. Br J Cancer. 47(2): 175–185. PMCID: PMC2011268, 1983
• Ijiri K and C. S. Potten, Further studies on the response of intestinal crypt cells of different hierarchical status to eighteen different cytotoxic agents. Br J Cancer. 55(2): 113–123. PMCID: PMC2002086, 1987
• Ikuno N, Soda H, Watanabe M, Oka M, Irinotecan (CPT-11) and characersitic mucosal changes in the mouse ileum and cecum, J Natl Cancer, Inst 87(24):1876-83, 1995
• Inomata A, Horii I, Suzuki K, 5-Fluorouracil induced intestinal toxicity: what determines the severity of damage to murine intestinal crypt epithelia?, Toxicol Lett 133(2-3):231-40, 2002
• Kalaskar AR, Management of Chemotherapy Induced Dysgeusia: An Important Step Towards Nutritional Rehabilitation. Int J Phys Med Rehabil 2:198. doi:10.4172/2329-9096.1000198, 2014
• Keefe DM, Brealey J, Goland GJ, Cummins AG, Small intestine. Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans, Gut;47:632-637 doi:10.1136/gut.47.5.632, 2000
• Keefe DMK, Cummins AG, Dale BM, Kotasek D, Robbt TA, Sage RE, Effect of high-dose chemotherapy on intestinal permeability in humans, Clinical Science 92, 385-389 (Printed in Great Britain) 385, 1997
• Keefe DMK, Gastrointestinal mucositis: a new biological model, Supportive Care in Cancer, Volume 12, Issue 1, pp 6–9, DOI: 10.1007/s00520-003-0550-9, Jan 2004
• Kim JW, Cha Y, Su-Jung K, Sae-Won H, Do-Youn O, Se-Hoon L, Dong-Wan K, Seock-Ah I, Tae-You K, Dae Seog H, Yung-Jue B, Association of oral mucositis with quality of life and symptom clusters in patients with solid tumors receiving chemotherapy, Support Care Cancer 20:395–403, DOI 10.1007/s00520-011-1126-8, 2012
• Kishi S, Cheng C, French D, Pei D, Das S, Cook EH, Hijiya N, Rizzari C, Rosner GL, Frudakis T, Pui CH, Evans WE, Relling MV, Ancestry and pharmacogenetics of antileukemic drug toxicity, Blood 109:4151-4157; doi:10.1182/blood-2006-10-054528, 2007
• Maeda T, Miyazono Y, Ito K, Hamada K, Sekine S, Horie T, Oxidative stress and enhanced paracellular permeability in the small intestine of methotrexate-treated rats, Cancer Chemother Pharmacol 65:1117–1123, DOI 10.1007/s00280-009-1119-1, 2010
• McLeod HL, Sargent DJ, Marsh S, Green EM, King CR, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Thibodeau SN, Grothey A, Morton RF, Goldberg RM, Pharmacogenetic Predictors of Adverse Events and Response to Chemotherapy in Metastatic Colorectal Cancer: Results From North American Gastrointestinal Intergroup Trial N9741, J Clin Oncol 28:3227-3233, 2010
• Nie X, Liu D, Li Q, Bai C, Journal of Geriatric Oncology, Volume 4, Issue 4, Pages 334–339, Predicting chemotherapy toxicity in older adults with lung cancer, doi:10.1016/j.jgo.2013.05.002, 2013
• Al-Dasooqi N, Gibson R, Bowen J, Logan R, Stringer A, Keefe D, Matrix Metalloproteinases Play A Pivotal Role In The Development Of Alimentary Tract Mucositis, Proceedings of the Sydney Cancer Conference, held at the University of Sydney, New South Wales 14-16, July 2010
• Rosmarin D, Palles C, Church D, Domingo E, et al., Genetic Markers of Toxicity From Capecitabine and Other Fluorouracil-Based Regimens: Investigation in the QUASAR2 Study, Systematic Review, and Meta-Analysis, JCO, vol. 32 no. 10 1031-1039, 2014
• Rubenstein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein J, Elting LS, Fox PC, Cooksley C, Sonis ST, Clinical Practice Guidelines for the Prevention and Treatment of Cancer Therapy–Induced Oral and Gastrointestinal Mucositis, Cancer;100(9Suppl):2026–2046, 2004
• Russo F, Linsalata M, Clemente C, D’Attoma B, Orlando A, Campanella G, Giotta F, Riezzo G, The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study, Russo et al. BMC Cancer, 13:56, 2013
• Simon RM, Genomic Clinical Trials and Predictive Medicine, Practical Guides to Biostatistics and Epidemiology, Publisher: Cambridge University Press, Print Publication Year:2013, Online Publication date:February 2013, Online ISBN:9781139026451, Hardback ISBN:9781107008809, Paperback ISBN:9781107401358; Book DOI: http://dx.doi.org/10.1017/CBO9781139026451, 2013
• Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients.Cancer.;100:1995–2025, 2004
• Stringer AM, Gibson RJ, Bowen JM, Keefe DMK, Chemotherapy-Induced Modifications to Gastrointestinal Microflora: Evidence and Implications of Change, Current Drug Metabolism, 10, 79-83, 2009
• Takasuna K, Hagiwara T, Watanabe K, Onese S, Yoshida S, Kumazawa E, Nagai E, Kamataki T, Optimal antidiarrheal treatemtn for antitumor agent irinotecan hydrochloride (CPT-11)-induced delayed diarrhea, Cancer Chemoter Pharmacol :1-10, 2006
• Tooley KL, Howarth GS, Lymn KA, Butler RN, Optimization of the non-invasive 13C-sucrose breath test in a rat model of methotrexate-induced mucositis, Cancer Chemother Pharmacol, 65:913–921, DOI 10.1007/s00280-009-1098-2, 2010
• Tooley K, Howarth G, Butler RN, Mucositis and non-invasive markers of small intestinal function, Cancer Biology and Therapy 8:9, 753-758, 1 May 2009
• Triantafyllou K, Dervenoulas J, Tsirigotis P, Ladas SD, The nature of small intestinal mucositis: a video-capsule endoscopy study, Supportive Care in Cancer, Volume 16, Issue 10, pp 1173–1178, October 2008
• Verburg M, Renes IB, Meijer HP, Taminiau JA, Buller HA, Einerhand AW, Dekker J, Selective sparing of goblet cells and paneth cells in the intestine of metothrexate-treated rats, Am J Physiol Gastrointest Liver Physiol 279(5):G1037-47, 2000
• Wang Y, Xuedong Z, Xin X, Journal of the Formosan Medical Association, Volume 114, Issue 4, Pages 297–299, Open Access Perspectives, Oral microbiota: An overlooked etiology for chemotherapy-induced oral mucositis?, , doi:10.1016/j.jfma.2013.10.014, April 2015
• Wintrobe’s Clinical Hematology, Thirteenth Edition, by John P. Greer (Author, Editor), Daniel A. Arber (Editor), Bertil Glader (Editor), ISBN-13: 978-1451172683, 2014
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Article Title: MUCOSITIS PATHOLOGY IN CHEMOTHERAPY INDUCED DIGESTIVE TOXICITY
Authors: Alciona Sasu*1,2, Mircea Onel1,2, Cornel Balta3, Cristina Ghib-Para1, Eftimie Miutescu4, Coralia Cotoraci1,2
Affiliation: 1 “Vasile Goldiş” Western University, Arad, Faculty of Medicine, Hematology Department
2 Emergency Clinical County Hospital of Arad, Hematology Clinic
3 “Vasile Goldiş” Western University, Arad, Institute of Life Sciences
4 “Vasile Goldiş” Western University, Arad, Faculty of Medicine, Gastroenterology Department
Abstract: Cytostatic chemotherapy can produce toxicity in the digestive tract at standard doses, in regimens given for various malignancies. Mucositis or gastrointestinal mucosal chemotherapy toxicity decreases the oncology patient’s quality of life and often leads to chemotherapy dose-reduction or even its discontinuation. This paper has two objectives: to emphasize a synthesis of data from the literature on the manifestation and pathogenesis of mucositis and, secondly, to present a study on the clinical mucositis on a group of patients receiving chemotherapy. The results showed that 61% of applications of chemotherapy are accompanied by digestive toxicity and each patient has at least one episode of nausea during cytostatic therapy. Understanding the mechanisms of mucositis allow the clinician to have a complex approach to the oncological patient receiving chemotherapy and find adjuvant substances that prevent or reduce this type of toxicity.
Keywords: mucositis, chemotherapy, gastrointestinal tract, intestinal toxicity, histopathology
References: • Al-Azri AR, RJ Gibson, DMK Keefe, RM Logan, Matrix metalloproteinases: do they play a role in mucosal pathology of the oral cavity?, Oral Diseases doi:10.1111/odi.12023, 2012
• Al-Dasooqi N, Bowen J, Gibson R, Stringer A, Logan R, Keefe D, Irinotecan-induced mucositis encompasses changes in intestinal and colonic cell kinetics and this is associated with altered extracellular matrix component expression, Journal of Gastroenterology and Hepatology, 25:A2-A2, October 2010
• Al-Dasooqi N, Bowen JM, Gibson RJ, Logan RM, Stringer AM, Keefe DM, Irinotecan-induced alterations in intestinal cell kinetics and extracellular matrix component expression in the dark agouti rat, Int. J. Exp. Path., doi: 10.1111/j.1365-2613.2011.00771.x, 2011
• Al-Dasooqi N, Gibson RJ, Bowen JM, Logan RM, Stringer AM, Keefe DM, Matrix metalloproteinases are possible mediators for the development of alimentary tract mucositis in the dark agouti rat, Experimental Biology and Medicine; 235: 1244–1256. DOI: 10.1258/ebm.2010.010082, 2010
• Beijnen J, Drug interactions in oncology, The Lancet Oncology, Volume 5, Issue 8, Pages 489–496, 2004
• Boige V, Mendiboure J, Pignon JP, et al., Pharmacogenetic Assessment of Toxicity and Outcome in Patients With Metastatic Colorectal Cancer Treated With LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05, JCO vol. 28 no. 15 2556-2564, 2010
• Bommu P, Nanjan CMJ, Joghee NM, Nataraj SM, Bhojraj S, Phyllanthus maderaspatensis, a dietary supplement for the amelioration of adriamycin-induced toxicity and oxidative stress in mice, J Nat Med. 2008 Apr;62(2):149-54. doi: 10.1007/s11418-007-0204-1. Epub 2007 Oct 24.
• Boussios S, Pentheroudakis G, Katsanos K, Pavlidisa N, Systemic treatment-induced gastrointestinal toxicity: incidence, clinical presentation and management, Ann Gastroenterol.; 25(2): 106–118. PMCID: PMC3959393, 2012
• Bowen JM, Gibson RJ, Keefe DM, Cummins AG, Cytotoxic chemotherapy upregulates pro‐apoptotic Bax and Bak in the small intestine of rats and humans, Pathology, Volume 37, Issue 1, 2005
• Bressana V, Stevaninb S, Bianchic M, Aleoc G, Bagnascoc A, Sassoc L, Cancer Treatment Reviews, Volume 45, Pages 105–119, Systematic or Meta-analysis Studies, The effects of swallowing disorders, dysgeusia, oral mucositis and xerostomia on nutritional status, oral intake and weight loss in head and neck cancer patients: A systematic review, , doi:10.1016/j.ctrv.2016.03.006, April 2016
• Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010) U.S.DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Cancer Institute, http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf, accessed 5 May 2016
• Cunningham D, Morgan RJ, Mills PR, Nelson LM, Toner PG, Soukop M, McArdle CS, Russell RI, Functional and structural changes of the human proximal small intestine after cytotoxic therapy, J Clin Pathol 38(3): 265-70, 1985
• Das J, Ghosh J, Manna P, Sil PC, Taurine protects rat testes against doxorubicin-induced oxidative stress as well as p53, Fas and caspase 12-mediated apoptosis, Amino Acids 42:1839–1855; DOI 10.1007/s00726-011-0904-4, 2012
• Di Palma M, Prise en charge des mucites chez les patients traitées pour un cancer du sein Groupe de travail : M. Di Palma, J.-P. Durand, L. Juhel, F. Scotte´ , C. Villanueva, Oncologie ISSN 1292-3818, 2009
• Duncan M, Grant G, Oral and intestinal mucositis — causes and possible treatments, Alimentary Pharmacologics and Therapeutics, Volume 18, Issue 9, Pages 853–874, DOI: 10.1046/j.1365-2036.2003.01784.x, Nov 2003
• Engelking C, Rutledge DN, Ippoliti C, Neumann J, Hogan CM. Cancer related diarrhea: a neglected cause of cancer-related symptom distress. Oncol Nurs Forum; 25:859-860, 1998
• Fijlstra M, Rings EHHM, van Dijk TH, Plösch T, Verkade HJ, Tissing WJE, Continuous enteral administration can overcome the limited capacity to absorb glucose in rats with methotrexate-induced gastrointestinal mucositis, Supportive Care in Cancer, Volume 21, Issue 3, pp 863–871, March 2013
• Freter CE, Perry MC, Systemic therapy. In Abelofff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG (eds) Abeloff’s Clinical Oncology. Fourth Edition, Churchill Livingstone Elsevier, Phildelphia PA 2008: 449- 483, 2008
• Gibson RJ, Bowen JM, Keefe DMK, Technological advances in mucositis research: New insights and new issues, Cancer Treatment Reviews; 34, 476– 482, 2008
• Gibson RJ, Cummins AG, Bowen JM, Logan RM, Healey T, Keefe DM, Apoptosis occurs early in the basal layer of the oral mucosa following cancer chemotherapy, Asia–Pacific Journal of Clinical Oncology; 2: 39–49, 2006
• Gibson RJ, Bowen JM, Inglis MR, Cummins AG, Keefe DMK, Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer, DOI: 10.1046/j.1440-1746.2003.03136.x, JGHF, Volume 18, Issue 9, Pages 1095–1100, September 2003
• Gibson RJ, Keefe DMK, Thompson FM, Clarke JM, Goland GJ, Cummins AG, Effect of Interleukin-11 on Ameliorating Intestinal Damage After Methotrexate Treatment of Breast Cancer in Rats, Digestive Diseases and Sciences, Volume 47, Issue 12, pp 2751–2757, Dec 2002
• Herbers AH, de Haan AF, van der Velden WJ, Donnelly JP, Blijlevens NM, Mucositis not neutropenia determines bacteremia among hematopoietic stem cell transplant recipients, Transpl Infect Dis. 2014 Apr;16(2):279-85. doi: 10.1111/tid.12195. Epub 2014 Mar 13
• Hoffman R, Benz EJ, Silberstein LE, Heslop H, Weitz J, Anastasi J. Hematology, Basic Principles and Practice. 6th Edition, Churchill Livingstone Title
ISBN: 978-1-4377-2928-3, 2384 pages, 2013
• Hurria A, Togawa K, Mohile SG, Owusu C, Klepin D, Gross C, Lichtman SM, Katheria V, Klapper S, Tew WP. Predicting Chemotherapy Toxicity in Older Adults with Cancer: A Prospective 500 Patient Multicenter Study [Abstract 9001]. American Society of Clinical Oncology, 2010
• Ijiri K and C. S. Potten, Response of intestinal cells of differing topographical and hierarchical status to ten cytotoxic drugs and five sources of radiation. Br J Cancer. 47(2): 175–185. PMCID: PMC2011268, 1983
• Ijiri K and C. S. Potten, Further studies on the response of intestinal crypt cells of different hierarchical status to eighteen different cytotoxic agents. Br J Cancer. 55(2): 113–123. PMCID: PMC2002086, 1987
• Ikuno N, Soda H, Watanabe M, Oka M, Irinotecan (CPT-11) and characersitic mucosal changes in the mouse ileum and cecum, J Natl Cancer, Inst 87(24):1876-83, 1995
• Inomata A, Horii I, Suzuki K, 5-Fluorouracil induced intestinal toxicity: what determines the severity of damage to murine intestinal crypt epithelia?, Toxicol Lett 133(2-3):231-40, 2002
• Kalaskar AR, Management of Chemotherapy Induced Dysgeusia: An Important Step Towards Nutritional Rehabilitation. Int J Phys Med Rehabil 2:198. doi:10.4172/2329-9096.1000198, 2014
• Keefe DM, Brealey J, Goland GJ, Cummins AG, Small intestine. Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans, Gut;47:632-637 doi:10.1136/gut.47.5.632, 2000
• Keefe DMK, Cummins AG, Dale BM, Kotasek D, Robbt TA, Sage RE, Effect of high-dose chemotherapy on intestinal permeability in humans, Clinical Science 92, 385-389 (Printed in Great Britain) 385, 1997
• Keefe DMK, Gastrointestinal mucositis: a new biological model, Supportive Care in Cancer, Volume 12, Issue 1, pp 6–9, DOI: 10.1007/s00520-003-0550-9, Jan 2004
• Kim JW, Cha Y, Su-Jung K, Sae-Won H, Do-Youn O, Se-Hoon L, Dong-Wan K, Seock-Ah I, Tae-You K, Dae Seog H, Yung-Jue B, Association of oral mucositis with quality of life and symptom clusters in patients with solid tumors receiving chemotherapy, Support Care Cancer 20:395–403, DOI 10.1007/s00520-011-1126-8, 2012
• Kishi S, Cheng C, French D, Pei D, Das S, Cook EH, Hijiya N, Rizzari C, Rosner GL, Frudakis T, Pui CH, Evans WE, Relling MV, Ancestry and pharmacogenetics of antileukemic drug toxicity, Blood 109:4151-4157; doi:10.1182/blood-2006-10-054528, 2007
• Maeda T, Miyazono Y, Ito K, Hamada K, Sekine S, Horie T, Oxidative stress and enhanced paracellular permeability in the small intestine of methotrexate-treated rats, Cancer Chemother Pharmacol 65:1117–1123, DOI 10.1007/s00280-009-1119-1, 2010
• McLeod HL, Sargent DJ, Marsh S, Green EM, King CR, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Thibodeau SN, Grothey A, Morton RF, Goldberg RM, Pharmacogenetic Predictors of Adverse Events and Response to Chemotherapy in Metastatic Colorectal Cancer: Results From North American Gastrointestinal Intergroup Trial N9741, J Clin Oncol 28:3227-3233, 2010
• Nie X, Liu D, Li Q, Bai C, Journal of Geriatric Oncology, Volume 4, Issue 4, Pages 334–339, Predicting chemotherapy toxicity in older adults with lung cancer, doi:10.1016/j.jgo.2013.05.002, 2013
• Al-Dasooqi N, Gibson R, Bowen J, Logan R, Stringer A, Keefe D, Matrix Metalloproteinases Play A Pivotal Role In The Development Of Alimentary Tract Mucositis, Proceedings of the Sydney Cancer Conference, held at the University of Sydney, New South Wales 14-16, July 2010
• Rosmarin D, Palles C, Church D, Domingo E, et al., Genetic Markers of Toxicity From Capecitabine and Other Fluorouracil-Based Regimens: Investigation in the QUASAR2 Study, Systematic Review, and Meta-Analysis, JCO, vol. 32 no. 10 1031-1039, 2014
• Rubenstein EB, Peterson DE, Schubert M, Keefe D, McGuire D, Epstein J, Elting LS, Fox PC, Cooksley C, Sonis ST, Clinical Practice Guidelines for the Prevention and Treatment of Cancer Therapy–Induced Oral and Gastrointestinal Mucositis, Cancer;100(9Suppl):2026–2046, 2004
• Russo F, Linsalata M, Clemente C, D’Attoma B, Orlando A, Campanella G, Giotta F, Riezzo G, The effects of fluorouracil, epirubicin, and cyclophosphamide (FEC60) on the intestinal barrier function and gut peptides in breast cancer patients: an observational study, Russo et al. BMC Cancer, 13:56, 2013
• Simon RM, Genomic Clinical Trials and Predictive Medicine, Practical Guides to Biostatistics and Epidemiology, Publisher: Cambridge University Press, Print Publication Year:2013, Online Publication date:February 2013, Online ISBN:9781139026451, Hardback ISBN:9781107008809, Paperback ISBN:9781107401358; Book DOI: http://dx.doi.org/10.1017/CBO9781139026451, 2013
• Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients.Cancer.;100:1995–2025, 2004
• Stringer AM, Gibson RJ, Bowen JM, Keefe DMK, Chemotherapy-Induced Modifications to Gastrointestinal Microflora: Evidence and Implications of Change, Current Drug Metabolism, 10, 79-83, 2009
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