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Title: Jurnal Medical Aradean (Arad Medical Journal)
Abbreviated title: J. Med. Ar.
Publisher: "Vasile Goldis" University Press
Owner: Western University "Vasile Goldis" Arad, Romania
ISSN: 1224-3744
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HEMATOLOGICAL TOXICITY AFTER EPIRUBICIN THERAPY AND THE INFLUENCE OF SILYMARIN ON THE BOOD PARAMETERS PDF Print E-mail

HEMATOLOGICAL TOXICITY AFTER EPIRUBICIN THERAPY AND THE INFLUENCE OF SILYMARIN ON THE BOOD PARAMETERS

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Title:HEMATOLOGICAL TOXICITY AFTER EPIRUBICIN THERAPY AND THE INFLUENCE OF SILYMARIN ON THE BOOD PARAMETERS
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Article_Title:HEMATOLOGICAL TOXICITY AFTER EPIRUBICIN THERAPY AND THE INFLUENCE OF SILYMARIN ON THE BOOD PARAMETERS
Authors:Alciona Sasu*1, Hildegard Herman2*, Mircea Onel1, Cristina Ghib-Para1, Eftimie Miutescu3, Coralia Cotoraci1
Affiliation:1 “Vasile Goldiş” Western University, Arad, Faculty of Medicine, Hematology Department
2 “Vasile Goldiş” Western University, Arad, Institute of Life Sciences
3 “Vasile Goldiş” Western University, Arad, Faculty of Medicine, Gastroenterology Department
Abstract:Epirubicin is a semisynthetic derivate of doxorubicin, used in various antineoplastic therapy regimens. Toxic effects of epirubicin are considered milder than those from other anthracycline drugs. One of the most common toxicity is myelosuppression. The current study aims at observing the hematologic toxicity in mice treated with epirubicin and the changes in complete blood count induced by the administration of silymarin. The results described a statistically significant increase in the number of leukocytes and decrease in red blood cell parameters in the group treated with epirubicin compared to the control group. We also described an increase in red cell parameters in the groups treated with silymarin, alone or combined with epirubicin, compared to the control group. These studies require additional research. Epirubicin, as a cytotoxic agent, may induce transient myelosuppression, which require careful patient monitoring.
Keywords:complete blood count, epirubicin, hematological toxicity, silymarin, leukopenia
References:• Adams VR, Adverse events associated with chemotherapy for common cancers, Pharmacotherapy, (7 Pt 2):96S-103S, PMID:10905684, 2000
• Airley R Cancer chemotherapy – Basic science to the clinic, Wiley-Blackwell, ISBN 978-0-470-09254-5 (HB) – ISBN 978-0-470-09255-2 (PB), pg 79-86, 2009
• Anghelache L, Marinescu B, Isvoranu G, Crînganu D, Niculae A, Bratu O, Cytostatic Therapy on Tumor Bearing Mice: Biochemical and Hematological Aspects, Modern Medicine. Vol. 23, No. 1 : 26-32, 2016
• Boussios S, Pentheroudakisa G, Katsanosb K, Pavlidisa N, Systemic treatment-induced gastrointestinal toxicity: incidence, clinical presentation and management, Annals of Gastroenterology, 25, 106-118, 2012
• Cousin S, Le Rhun E, Mailliez A, Fournier C, Bonneterre J, Febrile neutropenia incidence and hematological toxicity with the FEC100-docetaxel regimen in the treatment of early-stage breast cancer, Bull Cancer.; 99(7-8):75-80. doi: 10.1684/bdc.2012.1607, 2012
• Dragu ER, Chioaru BL, Sebe IT, Lascãr I, Coman OA, Experimenting on LAB rodents - ethical principles, Medicina Modernã; 22(3):264-268, 2015
• George JN, Section Editor, Lawrence Leung LK, Pathophysiology of acquired TTP and other primary thrombotic microangiopathies (TMAs), UptoDate, 2016, http://www.uptodate.com/contents/pathophysiology-of-acquired-ttp-and-other-primary-thrombotic-microangiopathies-tmas
• Hassett MJ, O'Malley AJ, Pakes JR, et al. Frequency and cost of chemotherapy-related serious adverse effects in a population sample of women with breast cancer. J Natl Cancer Inst; 98 (16): 1108-17, 2006 August 16
• http 1- http://genome.cshlp.org/content/15/12/1706.full; accessed October 2015.
• Ishii T, Miyazawa M, Takanashi Y, Tanigawa M, Yasuda K, Onouchi H, Kawabe N, Mitsushita J, Hartman PS, Ishii N. Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion. Redox Biol.; 2:679-85, doi: 10.1016/j.redox.2014.05.001, 2014
• Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M, “Silymarin”, a Promising Pharmacological Agent for Treatment of Diseases, Iranian Journal of Basic Medical Sciences Vol. 14, No. 4, 308-317, July-Aug 2011
• Karimi GH, Hassanzadeh M, Mehri S, Protective effects of Silymarin against free radical-induced erythrocyte lysis. J Alternat Complement Med; 3, 2006
• Launchbury AP, Habboubit N, Controversy, Epirubicin and doxorubicin: a comparison of their characteristics, therapeutic activity and toxicity Cancer Treatment Reviews, 19,197-228, 1993
• Liou SY, Stephens JM, Carpiuc KT, Feng W, Botteman MF, Hay JW, Economic Burden of Haematological Adverse Effects in Cancer Patients: A Systematic Review, Clinical Drug Investigation™, Disclosures, Clin Drug Invest.;27(6):381-396, 2007
• Lyman GH, Berndt ER, Kallich JD, et al. The economic burden of anemia in cancer patients receiving chemotherapy. Value Health, 8 (2): 149-56, 2005
• Lyman GH, Michels SL, Reynolds MW, Barron R, Tomic KS, Yu J, Risk of mortality in patients with cancer who experience febrile neutropenia, Cancer. 2010 Dec 1;116(23):5555-63. doi: 10.1002/cncr.25332, Epub 2010
• Lymana GL, Abellab E, Pettengellc R, Critical Reviews in Oncology/Hematology, Volume 90, Issue 3, Pages 190–199, Risk factors for febrile neutropenia among patients with cancer receiving chemotherapy: A systematic review, , doi:10.1016/j.critrevonc.2013.12.006, June 2014
• Pernkopf I, Tesch G, Dempe K, Kletzl H, Schüller J, Czejka M, Binding of epirubicin to human plasma protein and erythrocytes: interaction with the cytoprotective amifostine, Pharmazie.;51(11):897-901, 1996
• Prado CMM, Lima ISF, Baracos VE, Bies RS, McCargar LJ, Reiman T, Mackey JR, Kuzma M, Damaraju VL, Sawyer MB, An exploratory study of body composition as a determinant of epirubicin pharmacokinetics and toxicity, Cancer Chemother , Pharmacol, 67:93–101, DOI 10.1007/s00280-010-1288-y, 2011
• Psotová J, Chlopčíková S, Miketová P, Hrbáč J, Šimánek V, Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. part III. apigenin, baicalelin, kaempherol, luteolin and quercetin. Phytother Res.; 18:516-521, 2004
• Scotte F, Fabre E, Medioni J, Combe P, Angelergues A, Thibault C, Oudard S, Elaidi RT, Deleterious joint effect of fatigue and anemia in cancer patients treated with chemotherapy, European Journal of Cancer, Volume 51, Supplement 3, September 2015, Pages S226–S227, Abstracts from the European Cancer Congress 2015, Poster Session (Sunday, 27 September), 1568, , doi:10.1016/S0959-8049(16)30657-8, 2015
• Sena A, Karakasb E, Bilaloglua R, Genotoxic Effect of Epirubicin in Mouse Bone Marrow in vivo, Z. Naturforsch. 65 c, 211 – 217, 2010
• Simmons D, The use of animal models in studying genetic disease: transgenesis and induced mutation. Nature Education.; 1(1):70, 2008
• Smit EF, Berendsen HH, Piers DA, Smeets J, Riva A, Postmus PE, A phase II study of high dose epirubicin in unresectable non small cell lung cancer, Br J Cancer.;65:405–408, 1992
• Strausa DJ, Treatment of Anemia with Erythropoietic Agents in Patients with Hematologic Malignancies, Supportive Cancer Therapy, Volume 2, Issue 4, Pages 215–224, doi:10.3816/SCT.2005.n.014, July 2005
• Thurnher D, Kletzmayr J, Formanek M, Quint C, Czerny C, Burian M, Kornek G, Chemotherapy-related hemolytic-uremic syndrome following treatment of a carcinoma of the nasopharynx, Oncology.;61(2):143-6, 2001
• Ulas A, Silay K, Akinci S, Akinci BM, Sendur AM, Dede DS, Polat YH, Yalcin B, Thrombotic thrombocytopenic purpura following salvage chemotherapy with paclitaxel, ifosfamide and cisplatin in a patient with a refractory germ cell tumor: A case report and review of the literature, Oncol Lett.10(4): 2223–2226. doi: 10.3892/ol.2015.3338, PMCID: PMC4579812, 2015
• Wachters FM, van Putten JWG, Kramer H, Erjavec Z, Eppinga P, Strijbos JH, de Leede GPJ, Boezen HM, de Vries EGE, Groen HJM, First-line gemcitabine with cisplatin or epirubicin in advanced non-small-cell lung cancer: a phase III trial, Br J Cancer.; 89(7): 1192–1199. doi: 10.1038/sj.bjc.6601283, 2003
• Wang L, Barron R, Baser O, Langeberg WJ, Dale DC, Brief Reports Cancer Chemotherapy Treatment Patterns and Febrile Neutropenia in the US Veterans Health Administration, Value in Health, Volume 17, Issue 6, Pages 739–743, doi:10.1016/j.jval.2014.06.009, September 2014
• Wils J, Utama I, Sala L, Smeets J, Riva A, Phase II study of high-dose epirubicin in non-small cell lung cancer. Eur J Cancer.;26:1140–1141, 1990
• Wintrobe's Clinical Hematology, Thirteenth Edition, by John P. Greer (Author, Editor), Daniel A. Arber (Editor), Bertil Glader (Editor), ISBN-13: 978-1451172683, 2014
• Yuvaraj S, Sasa M, Honda J, Takahashi A, Uno S, Kamatani N, Kubo M, Nakamura Y, Zembutsu H, Genome-wide association study of epirubicin-induced leukopenia in Japanese patients, Pharmacogenetics and Genomics: Volume 21 - Issue 9 - p 552–558, doi: 10.1097/FPC.0b013e328348e48f, September 2011
• Zaremba T, Thomas H, Cole M, Plummer ER, Curtin NJ, Doxorubicin-induced suppression of poly(ADP-ribose), polymerase-1 (PARP-1) activity and expression and its implication for PARP inhibitors in clinical trials, , Cancer Chemother Pharmacol.;66(4):807-12. doi: 10.1007/s00280-010-1359-0, 2010
• Zhu ZF1, Li-juan C, Rong L, Jing J, Yu L, Qiong X, Chun-lei Z, Li W, Song W, Zhi Y, Tripeptide tyroserleutide plus doxorubicin: therapeutic synergy, and side effect attenuation, *1,4, BMC Cancer, 8:342 doi:10.1186/1471-2407-8-342, 2008
Read_full_article:pdf/vol19/iss1/1 JMA 2016 - HEMATOLOGICAL TOXICITY AFTER EPIRUBICIN THERAPY , SASU ALCIONA.pdf
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Article Title:HEMATOLOGICAL TOXICITY AFTER EPIRUBICIN THERAPY AND THE INFLUENCE OF SILYMARIN ON THE BOOD PARAMETERS
Authors:Alciona Sasu*1, Hildegard Herman2*, Mircea Onel1, Cristina Ghib-Para1, Eftimie Miutescu3, Coralia Cotoraci1
Affiliation:1 “Vasile Goldiş” Western University, Arad, Faculty of Medicine, Hematology Department
2 “Vasile Goldiş” Western University, Arad, Institute of Life Sciences
3 “Vasile Goldiş” Western University, Arad, Faculty of Medicine, Gastroenterology Department
Abstract:Epirubicin is a semisynthetic derivate of doxorubicin, used in various antineoplastic therapy regimens. Toxic effects of epirubicin are considered milder than those from other anthracycline drugs. One of the most common toxicity is myelosuppression. The current study aims at observing the hematologic toxicity in mice treated with epirubicin and the changes in complete blood count induced by the administration of silymarin. The results described a statistically significant increase in the number of leukocytes and decrease in red blood cell parameters in the group treated with epirubicin compared to the control group. We also described an increase in red cell parameters in the groups treated with silymarin, alone or combined with epirubicin, compared to the control group. These studies require additional research. Epirubicin, as a cytotoxic agent, may induce transient myelosuppression, which require careful patient monitoring.
Keywords:complete blood count, epirubicin, hematological toxicity, silymarin, leukopenia
References:• Adams VR, Adverse events associated with chemotherapy for common cancers, Pharmacotherapy, (7 Pt 2):96S-103S, PMID:10905684, 2000
• Airley R Cancer chemotherapy – Basic science to the clinic, Wiley-Blackwell, ISBN 978-0-470-09254-5 (HB) – ISBN 978-0-470-09255-2 (PB), pg 79-86, 2009
• Anghelache L, Marinescu B, Isvoranu G, Crînganu D, Niculae A, Bratu O, Cytostatic Therapy on Tumor Bearing Mice: Biochemical and Hematological Aspects, Modern Medicine. Vol. 23, No. 1 : 26-32, 2016
• Boussios S, Pentheroudakisa G, Katsanosb K, Pavlidisa N, Systemic treatment-induced gastrointestinal toxicity: incidence, clinical presentation and management, Annals of Gastroenterology, 25, 106-118, 2012
• Cousin S, Le Rhun E, Mailliez A, Fournier C, Bonneterre J, Febrile neutropenia incidence and hematological toxicity with the FEC100-docetaxel regimen in the treatment of early-stage breast cancer, Bull Cancer.; 99(7-8):75-80. doi: 10.1684/bdc.2012.1607, 2012
• Dragu ER, Chioaru BL, Sebe IT, Lascãr I, Coman OA, Experimenting on LAB rodents - ethical principles, Medicina Modernã; 22(3):264-268, 2015
• George JN, Section Editor, Lawrence Leung LK, Pathophysiology of acquired TTP and other primary thrombotic microangiopathies (TMAs), UptoDate, 2016, http://www.uptodate.com/contents/pathophysiology-of-acquired-ttp-and-other-primary-thrombotic-microangiopathies-tmas
• Hassett MJ, O'Malley AJ, Pakes JR, et al. Frequency and cost of chemotherapy-related serious adverse effects in a population sample of women with breast cancer. J Natl Cancer Inst; 98 (16): 1108-17, 2006 August 16
• http 1- http://genome.cshlp.org/content/15/12/1706.full; accessed October 2015.
• Ishii T, Miyazawa M, Takanashi Y, Tanigawa M, Yasuda K, Onouchi H, Kawabe N, Mitsushita J, Hartman PS, Ishii N. Genetically induced oxidative stress in mice causes thrombocytosis, splenomegaly and placental angiodysplasia that leads to recurrent abortion. Redox Biol.; 2:679-85, doi: 10.1016/j.redox.2014.05.001, 2014
• Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M, “Silymarin”, a Promising Pharmacological Agent for Treatment of Diseases, Iranian Journal of Basic Medical Sciences Vol. 14, No. 4, 308-317, July-Aug 2011
• Karimi GH, Hassanzadeh M, Mehri S, Protective effects of Silymarin against free radical-induced erythrocyte lysis. J Alternat Complement Med; 3, 2006
• Launchbury AP, Habboubit N, Controversy, Epirubicin and doxorubicin: a comparison of their characteristics, therapeutic activity and toxicity Cancer Treatment Reviews, 19,197-228, 1993
• Liou SY, Stephens JM, Carpiuc KT, Feng W, Botteman MF, Hay JW, Economic Burden of Haematological Adverse Effects in Cancer Patients: A Systematic Review, Clinical Drug Investigation™, Disclosures, Clin Drug Invest.;27(6):381-396, 2007
• Lyman GH, Berndt ER, Kallich JD, et al. The economic burden of anemia in cancer patients receiving chemotherapy. Value Health, 8 (2): 149-56, 2005
• Lyman GH, Michels SL, Reynolds MW, Barron R, Tomic KS, Yu J, Risk of mortality in patients with cancer who experience febrile neutropenia, Cancer. 2010 Dec 1;116(23):5555-63. doi: 10.1002/cncr.25332, Epub 2010
• Lymana GL, Abellab E, Pettengellc R, Critical Reviews in Oncology/Hematology, Volume 90, Issue 3, Pages 190–199, Risk factors for febrile neutropenia among patients with cancer receiving chemotherapy: A systematic review, , doi:10.1016/j.critrevonc.2013.12.006, June 2014
• Pernkopf I, Tesch G, Dempe K, Kletzl H, Schüller J, Czejka M, Binding of epirubicin to human plasma protein and erythrocytes: interaction with the cytoprotective amifostine, Pharmazie.;51(11):897-901, 1996
• Prado CMM, Lima ISF, Baracos VE, Bies RS, McCargar LJ, Reiman T, Mackey JR, Kuzma M, Damaraju VL, Sawyer MB, An exploratory study of body composition as a determinant of epirubicin pharmacokinetics and toxicity, Cancer Chemother , Pharmacol, 67:93–101, DOI 10.1007/s00280-010-1288-y, 2011
• Psotová J, Chlopčíková S, Miketová P, Hrbáč J, Šimánek V, Chemoprotective effect of plant phenolics against anthracycline-induced toxicity on rat cardiomyocytes. part III. apigenin, baicalelin, kaempherol, luteolin and quercetin. Phytother Res.; 18:516-521, 2004
• Scotte F, Fabre E, Medioni J, Combe P, Angelergues A, Thibault C, Oudard S, Elaidi RT, Deleterious joint effect of fatigue and anemia in cancer patients treated with chemotherapy, European Journal of Cancer, Volume 51, Supplement 3, September 2015, Pages S226–S227, Abstracts from the European Cancer Congress 2015, Poster Session (Sunday, 27 September), 1568, , doi:10.1016/S0959-8049(16)30657-8, 2015
• Sena A, Karakasb E, Bilaloglua R, Genotoxic Effect of Epirubicin in Mouse Bone Marrow in vivo, Z. Naturforsch. 65 c, 211 – 217, 2010
• Simmons D, The use of animal models in studying genetic disease: transgenesis and induced mutation. Nature Education.; 1(1):70, 2008
• Smit EF, Berendsen HH, Piers DA, Smeets J, Riva A, Postmus PE, A phase II study of high dose epirubicin in unresectable non small cell lung cancer, Br J Cancer.;65:405–408, 1992
• Strausa DJ, Treatment of Anemia with Erythropoietic Agents in Patients with Hematologic Malignancies, Supportive Cancer Therapy, Volume 2, Issue 4, Pages 215–224, doi:10.3816/SCT.2005.n.014, July 2005
• Thurnher D, Kletzmayr J, Formanek M, Quint C, Czerny C, Burian M, Kornek G, Chemotherapy-related hemolytic-uremic syndrome following treatment of a carcinoma of the nasopharynx, Oncology.;61(2):143-6, 2001
• Ulas A, Silay K, Akinci S, Akinci BM, Sendur AM, Dede DS, Polat YH, Yalcin B, Thrombotic thrombocytopenic purpura following salvage chemotherapy with paclitaxel, ifosfamide and cisplatin in a patient with a refractory germ cell tumor: A case report and review of the literature, Oncol Lett.10(4): 2223–2226. doi: 10.3892/ol.2015.3338, PMCID: PMC4579812, 2015
• Wachters FM, van Putten JWG, Kramer H, Erjavec Z, Eppinga P, Strijbos JH, de Leede GPJ, Boezen HM, de Vries EGE, Groen HJM, First-line gemcitabine with cisplatin or epirubicin in advanced non-small-cell lung cancer: a phase III trial, Br J Cancer.; 89(7): 1192–1199. doi: 10.1038/sj.bjc.6601283, 2003
• Wang L, Barron R, Baser O, Langeberg WJ, Dale DC, Brief Reports Cancer Chemotherapy Treatment Patterns and Febrile Neutropenia in the US Veterans Health Administration, Value in Health, Volume 17, Issue 6, Pages 739–743, doi:10.1016/j.jval.2014.06.009, September 2014
• Wils J, Utama I, Sala L, Smeets J, Riva A, Phase II study of high-dose epirubicin in non-small cell lung cancer. Eur J Cancer.;26:1140–1141, 1990
• Wintrobe's Clinical Hematology, Thirteenth Edition, by John P. Greer (Author, Editor), Daniel A. Arber (Editor), Bertil Glader (Editor), ISBN-13: 978-1451172683, 2014
• Yuvaraj S, Sasa M, Honda J, Takahashi A, Uno S, Kamatani N, Kubo M, Nakamura Y, Zembutsu H, Genome-wide association study of epirubicin-induced leukopenia in Japanese patients, Pharmacogenetics and Genomics: Volume 21 - Issue 9 - p 552–558, doi: 10.1097/FPC.0b013e328348e48f, September 2011
• Zaremba T, Thomas H, Cole M, Plummer ER, Curtin NJ, Doxorubicin-induced suppression of poly(ADP-ribose), polymerase-1 (PARP-1) activity and expression and its implication for PARP inhibitors in clinical trials, , Cancer Chemother Pharmacol.;66(4):807-12. doi: 10.1007/s00280-010-1359-0, 2010
• Zhu ZF1, Li-juan C, Rong L, Jing J, Yu L, Qiong X, Chun-lei Z, Li W, Song W, Zhi Y, Tripeptide tyroserleutide plus doxorubicin: therapeutic synergy, and side effect attenuation, *1,4, BMC Cancer, 8:342 doi:10.1186/1471-2407-8-342, 2008
*Correspondence: