Efficacy of concomitant therapy with ademetionine in antitumor drug therapy: A review

Cover Page

Cite item

Full Text

Abstract

Liver injury caused by antitumor therapy is a common disorder in patients with malignancies. It is due to the introduction of new innovative drugs into the treatment, which significantly increases the duration and quality of life, but also the frequency of side effects with liver damage of varying severity. The rate of hepatotoxicity during chemotherapy ranges from 5% to 100%. The spectrum of morphological changes in the liver is diverse and includes acute and chronic liver injury with damage to hepatocytes and outcome in fibrosis. The clinical features of the diagnosis of various types, variants, and phenotypes of drug-induced liver injury in the chemotherapy of solid tumors and hematological malignancies are addressed. The article reviews the literature on concomitant treatment with ademetionine to reduce metabolic disorders and hepatic toxicity caused by cytotoxic therapy. Clinical and biochemical effects persist for a long time after treatment. The results of using ademetionine to correct clinical symptoms such as fatigue are described in detail. The presented data supports a practical revision of the role of concomitant therapy with ademetionine to prevent and reduce the manifestations of hepatotoxicity induced by polychemotherapy. This approach contributes to a personalized approach to patients with malignancies, thereby significantly improving medical care and increasing the duration and quality of life.

About the authors

Nikolai A. Ognerubov

Penza Institute for Advanced Training of Physicians – branch of the Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: ognerubov_n.a@mail.ru
ORCID iD: 0000-0003-4045-1247

D. Sci. (Med.), Cand. Sci. (Law), Prof.

Russian Federation, Penza

References

  1. Mehta N, Ozick LA, Lisa Anne Ozck, Gbadehan E. Drug-Induced Hepatotoxicity. Jul 08, 2022. Available at: https://emedicine.medscape.com/article/169814-overview?form=fpf. Accessed: 28.04.2024.
  2. Björnsson ES, Bergmann OM, Björnsson HK, et al. Incidence, Presentation, and Outcomes in Patients With Drug-Induced Liver Injury in the General Population of Iceland. Gastroenterology. 2013;144(7):1419-25, 1425.e1-3; quiz e19-20. doi: 10.1053/j.gastro.2013.02.006
  3. Reporting adverse drug reactions definitions of terms and criteria for their use. Geneva: CIOMS, 1999. 146 p.
  4. Periáñez-Párraga L, Martínez-López I, Ventayol-Bosch P, et al. Drug dosage recommendations in patients with chronic liver disease. Rev Esp Enferm Dig. 2012;104(4):165-84. doi: 10.4321/s1130-01082012000400002
  5. Mudd TW, Guddati AK. Management of hepatotoxicity of chemotherapy and targeted agents. Am J Cancer Res. 2021;11(7):3461-74.
  6. Colsky J, Greenspan EM, Warren TN. Hepatic fibrosis in children with acute leukemia after therapy with folic acid antagonists. AMA Arch Pathol. 1955;59:198-206.
  7. Hoofnagle JH, Björnsson ES. Drug-Induced Liver Injury – Types and Phenotypes. N Engl J Med. 2019;381(3):264-73. doi: 10.1056/NEJMra1816149
  8. Sharma A, Houshyar R, Bhosale P, et al. Chemotherapy induced liver abnormalities: an imaging perspective. Clin Mol Hepatol. 2014;20(3):317-26. doi: 10.3350/cmh.2014.20.3.317
  9. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Drug-Induced Liver Injury. J Hepatol. 2019;70(6):1222-61. doi: 10.1016/j.jhep.2019.02.014
  10. Almutairi AR, McBride A, Slack M, et al. Potential Immune-Related Adverse Events Associated With Monotherapy and Combination Therapy of Ipilimumab, Nivolumab, and Pembrolizumab for Advanced Melanoma: A Systematic Review and Meta-Analysis. Front Oncol. 2020;10:91. doi: 10.3389/fonc.2020.00091
  11. Cho YA, Han JM, Kang SY, et al. Analysis of Risk Factors for Hepatotoxicity Induced by Immune Checkpoint Inhibitors. J Immunother. 2021;44(1):16-21. doi: 10.1097/CJI.0000000000000347
  12. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373(1):23-34. doi: 10.1056/NEJMoa1504030
  13. Wang DY, Salem JE, Cohen JV, et al. Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncol. 2018;4(12):1721-8. doi: 10.1001/jamaoncol.2018.3923
  14. Wolchok JD, Neyns B, Linette G, et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol. 2010;11(2):155-64. doi: 10.1016/S1470-2045(09)70334-1
  15. Cohen JV, Dougan M, Zubiri L, et al. Liver biopsy findings in patients on immune checkpoint inhibitors. Mod Pathol. 2021;34(2):426-37. doi: 10.1038/s41379-020-00653-1
  16. Thomas R, Sebastian B, George T, et al. A review of the imaging manifestations of immune check point inhibitor toxicities. Clin Imaging. 2020;64:70-9. doi: 10.1016/j.clinimag.2020.04.007
  17. Tsung I, Dolan R, Lao CD, et al. Liver injury is most commonly due to hepatic metastases rather than drug hepatotoxicity during pembrolizumab immunotherapy. Aliment Pharmacol Ther. 2019;50(7):800-8. doi: 10.1111/apt.15413
  18. Andrade RJ, Lucena MI, Fernández MC, et al. Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Gastroenterology. 2005;129(2):512-21.
  19. Shen T, Liu Y, Shang J, et al. Incidence and Etiology of Drug-Induced Liver Injury in Mainland China. Gastroenterology. 2019;156(8):2230-41.e11. doi: 10.1053/j.gastro.2019.02.002
  20. Benić MS, Nežić L, Vujić-Aleksić V, Mititelu-Tartau L. Novel Therapies for the Treatment of Drug-Induced Liver Injury: A Systematic Review. Front Pharmacol. 2022;12:785790. doi: 10.3389/fphar.2021.785790
  21. Sakamori Y, Kim YH, Yoshida H, et al. Effect of liver toxicity on clinical outcome of patients with non-small-cell lung cancer treated with pemetrexed. Mol Clin Oncol. 2015;3(2):334-40. doi: 10.3892/mco.2014.452
  22. Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician. 2007;76(3):391-6.
  23. Larrey D, Pageaux GP. Genetic predisposition to drug-induced hepatotoxicity. J Hepatol. 1997;26(Suppl. 2):12-21. doi: 10.1016/s0168-8278(97)80492-8
  24. Казюлин А.Н., Вельшер Л.З., Бяхов М.Ю., Королева И.А. Эффективность сопроводительной терапии адеметионином (гептралом) при проведении противоопухолевой лекарственной терапии у больных с онкологическими заболеваниями различной локализации. Злокачественные опухоли. 2013;(3):16-34 [Kazyulin AN, Vel'sher LZ, Byakhov MYu, Koroleva IA. Efficiency of accompanying medication with ademetionine (HEPTRAL) during anticancer therapy in patients with cancer of various localization. Malignant Tumours. 2013;(3):16-34 (in Russian)]. doi: 10.18027/2224-5057-2013-3-16-34
  25. Björnsson E. Drug-induced liver injury: Hy's rule revisited. Clin Pharmacol Ther. 2006;79(6):521-8. doi: 10.1016/j.clpt.2006.02.012
  26. Imoto K, Kohjima M, Hioki T, et al. Clinical Features of Liver Injury Induced by Immune Checkpoint Inhibitors in Japanese Patients. Can J Gastroenterol Hepatol. 2019;2019:6391712. doi: 10.1155/2019/6391712
  27. Danan G, Teschke R. RUCAM in drug and herb induced liver injury: the update. Int J Mol Sci. 2016;17(1):14.
  28. Da Cunha T, Wu GY, Vaziri H. Immunotherapy-induced Hepatotoxicity: A Review. J Clin Transl Hepatol. 2022;10(6):1194-204. doi: 10.14218/JCTH.2022.00105
  29. LiverTox: clinical and research information on drug-induced liver injury. Bethesda, MD: National Institutes of Health. Available at: https://www.LiverTox.nih.gov. Accessed: 28.04.2024.
  30. Kleiner DE, Chalasani NP, Lee WM, et al. Drug-Induced Liver Injury Network (DILIN) Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations. Hepatology. 2014;59:661-70.
  31. Stine JG, Lewis JH. Current and Future Directions in the Treatment and Prevention of Drug-Induced Liver Injury: a Systematic Review. Expert Rev Gastroenterol Hepatol. 2016;10:517-36. doi: 10.1586/17474124.2016.1127756
  32. Mato JM, Lu SC. Role of S-adenosyl-L-methionine in liver health and injury. Hepatology. 2007;45(5):1306-12. doi: 10.1002/hep.21650
  33. Anstee QM, Day CP. S-adenosylmethionine (SAMe) therapy in liver disease: a review of current evidence and clinical utility. J Hepatol. 2012;57(5):1097-109. doi: 10.1016/j.jhep.2012.04.041
  34. Lu SC, Mato JM. S-adenosylmethionine in liver health, injury, and cancer. Physiol Rev. 2012;92(4):1515-42. doi: 10.1152/physrev.00047.2011
  35. Testino G, Leone S, Fagoonee S, Pellicano R. The role of adenosyl-methionine in alcoholic liver disease and intrahepatic cholestasis. Minerva Gastroenterol Dietol. 2018;64(3):187-9. doi: 10.23736/S1121-421X.18.02484-4
  36. Mora SI, García-Román J, Gómez-Ñañez I, García-Román R. Chronic Liver Diseases and the Potential Use of S-Adenosyl-L-Methionine as a Hepatoprotector. Eur J Gastroenterol Hepatol. 2018;30:893-900. doi: 10.1097/MEG.0000000000001141
  37. Ivashkin VT, Maevskaya MV, Kobalava ZD, et al. Open-label study of ademetionine for the treatment of intrahepatic cholestasis associated with alcoholic liver disease. Minerva Gastroenterol Dietol. 2018;64(3):208-19. doi: 10.23736/S1121-421X.18.02461-3
  38. Vincenzi B, Daniele S, Frezza AM, et al. The role of S-adenosylmethionine in preventing oxaliplatin-induced liver toxicity: a retrospective analysis in metastatic colorectal cancer patients treated with bevacizumab plus oxaliplatin-based regimen. Support Care Cancer. 2012;20(1):135-9. doi: 10.1007/s00520-010-1078-4
  39. Zainal Abidin MN, Omar MS, Islahudin F. et al. The survival impact of palliative chemotherapy dose modifications on metastatic colon cancer. BMC Cancer. 2022;22(1):731. doi: 10.1186/s12885-022-09831-7
  40. De Melo Gagliato D, Lei X, Giordano SH, et al. Impact of Delayed Neoadjuvant Systemic Chemotherapy on Overall Survival Among Patients with Breast Cancer. Oncologist. 2020;25(9):749-57. doi: 10.1634/theoncologist.2019-0744
  41. Santini D, Vincenzi B, Massacesi C, et al. S-adenosylmethionine (AdoMet) supplementation for treatment of chemotherapy-induced liver injury. Anticancer Res. 2003;23(6D):5173-9.
  42. Снеговой А.В., Ларионова В.Б., Зейналова П.А., и др. Окончательные результаты проспективной многоцентровой программы Р12-717 (применение Гептрала при хронической болезни печени, обусловленной лекарственно-индуцированным поражением печени вследствие химиотерапии). Вестник РОНЦ им. Н.Н. Блохина РАМН. 2016;27(2):142-56 [Snegovoy AV, Larionova VB, Zeynalova PA, et al. Final Results Prospective, Multicenter Program P12-717 (Same Application In Chronic Liver Disease, Conditionality Of Drug-Induced Liver Injury Due To Chemotherapy). Vestnik RONTs im. N.N. Blokhina RAMN. 2016;27(2):142-56 (in Russian)].
  43. Ларионова В.Б., Снеговой А.В. Возможности коррекции лекарственной печеночной токсичности при лечении больных с опухолями системы крови. Онкогематология. 2020;15(4):65-81 [Larionova VB, Snegovoy AV. Correction possibilities of drug-induced liver toxicity in the treatment of patients with blood system tumors. Oncohematology. 2020;15(4):65-81 (in Russian)]. doi: 10.17650/1818-8346-2020-15-4-65-81
  44. Guo T, Chang L, Xiao Y, Liu Q. S-adenosyl-L-methionine for the treatment of chronic liver disease: a systematic review and meta-analysis. PLoS One. 2015;10(3):e0122124. doi: 10.1371/journal.pone.0122124
  45. Fiorelli G. S-Adenosylmethionine in the treatment of intrahepatic cholestasis of chronic liver disease: a field trial. Cur Ther Res. 1999;60:335-48.
  46. Горбаков В.В., Галик В.П., Кириллов С.М. Опыт применения гептрала в лечении диффузных заболеваний печени. Терапевтический архив. 1998;70(10):82-6 [Gorbakov VV, Galik VP, Kirillov SM. Experience in heptral treatment of diffuse liver diseases. Terapevticheskii Arkhiv (Ter. Arkh.). 1998;70(10):82-6 (in Russian)].
  47. Ткаченко П.Е., Ивашкин В.Т., Маевская М.В. Коррекция гепатотоксичности, индуцированной противоопухолевой терапией. Злокачественные опухоли. 2023;13(3s2):69-82 [Tkachenko PE, Ivashkin VT, Maevskaia MV. Korrektsiia gepatotoksichnosti, indutsirovannoi protivoopukholevoi terapiei. Malignant Tumours. 2023;13(3s2):69-82 (in Russian)]. doi: 10.18027/2224-5057-2023-13-3s2-2-69-82
  48. Протоколы клинических рекомендаций поддерживающей терапии в онкологии. 4-е изд., перераб. и доп. М.: АБВ-пресс, 2020 [Protokoly klinicheskikh rekomendatsii podderzhivaiushchei terapii v onkologii. 4-e izd., pererab. i dop. Moscow: ABV-press, 2020 (in Russian)].
  49. Bower JE. Cancer-related fatigue – mechanisms, risk factors, and treatments. Nat Rev Clin Oncol. 2014;11(10):597-609. doi: 10.1038/nrclinonc.2014.127
  50. Райхельсон К.Л., Кондрашина Э.А. Адеметионин в лечении повышенной утомляемости/слабости при заболеваниях печени: систематический обзор. Терапевтический архив. 2019;91(2):134-42 [Raikhelson KL, Kondrashina EA. Ademethionine in the treatment of fatigue in liver diseases: a systematic review. Terapevticheskii Arkhiv (Ter. Arkh.). 2019;91(2):134-42 (in Russian)]. doi: 10.26442/00403660.2019.02.000130
  51. Thong MS, Mols F, Wang XS, et al. Quantifying fatigue in (long-term) colorectal cancer survivors: a study from the population-based patient reported outcomes following initial treatment and long term evaluation of survivorship registry. Eur J Cancer. 2013;49(8):1957-66. doi: 10.1016/j.ejca.2013.01.012
  52. Minton O, Stone P. A systematic review of the scales used for the measurement of cancer-related fatigue (CRF). Ann Oncol. 2009;20(1):17-25. doi: 10.1093/annonc/mdn537
  53. Lawrence DP, Kupelnick B, Miller K, et al. Evidence report on the occurrence, assessment, and treatment of fatigue in cancer patients. J Natl Cancer Inst Monogr. 2004;(32):40-50. doi: 10.1093/jncimonographs/lgh027
  54. Servaes P, Verhagen C, Bleijenberg G. Fatigue in cancer patients during and after treatment: prevalence, correlates and interventions. Eur J Cancer. 2002;38(1):27-43. doi: 10.1016/s0959-8049(01)00332-x
  55. Swain MG, Jones DEJ. Fatigue in chronic liver disease: New insights and therapeutic approaches. Liver Int. 2019;39(1):6-19. doi: 10.1111/liv.13919
  56. Jopson L, Dyson JK, Jones DE. Understanding and Treating Fatigue in Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis. Clin Liver Dis. 2016;20(1):131-42. doi: 10.1016/j.cld.2015.08.007
  57. Cauch-Dudek K, Abbey S, Stewart DE, Heathcote EJ. Fatigue in primary biliary cirrhosis. Gut. 1998;43(5):705-10. doi: 10.1136/gut.43.5.705
  58. Bower JE, Ganz PA, Desmond KA, et al. Fatigue in long-term breast carcinoma survivors: a longitudinal investigation. Cancer. 2006;106(4):751-8. doi: 10.1002/cncr.21671
  59. Wunsch E, Raszeja-Wyszomirska J, Barbier O, et al. Effect of S-adenosyl-L-methionine on liver biochemistry and quality of life in patients with primary biliary cholangitis treated with ursodeoxycholic acid. A prospective, open label pilot study. J Gastrointestin Liver Dis. 2018;27(3):273-9. doi: 10.15403/jgld.2014.1121.273.icz
  60. Onorato A, Napolitano A, Spoto S, et al. S-Adenosylmethionine Supplementation May Reduce Cancer-Related Fatigue: A Prospective Evaluation Using the FACIT-F Questionnaire in Colon Cancer Patients Undergoing Oxaliplatin-Based Chemotherapy Regimens. Chemotherapy. 2021;66(5-6):161-8. doi: 10.1159/000517376
  61. Virukalpattigopalratnam MP, Singh T, Ravishankar AC. Heptral (ademetionine) in patients with intrahepatic cholestasis in chronic liver disease due to non-alcoholic liver disease: results of a multicentre observational study in India. J Indian Med Assoc. 2013;111(12):856-9.
  62. Frezza M, Surrenti C, Manzillo G, et al. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. Gastroenterology. 1990;99:211-15.
  63. Ларионова В.Б., Зейналова П.А., Снеговой А.В. Предварительные результаты проспективной многоцентровой наблюдательной программы оценки популяции пациентов с ЛИПП вследствие химиотерапии, получающих гептрал в РФ. Вестник РОНЦ им. Н.Н. Блохина РАМН. 2015;26:41-50 [Larionova VB, Zeinalova PA, Snegovoi AV. Predvaritel'nye rezul'taty prospektivnoi mnogotsentrovoi nabliudatel'noi programmy otsenki populiatsii patsientov s LIPP vsledstvie khimioterapii, poluchaiushchikh geptral v RF. Vestnik RONTs im. N.N. Blokhina RAMN. 2015;26:41-50 (in Russian)].
  64. Perlamutrov Y, Bakulev A, Korsunskaya I, et al. Ademetionine in treatment of drug induced liver injury: an observational study in Russian patients, receiving immunosuppressive therapy for psoriasis. IJPSR. 2014;5(12):5163-9. doi: 10.13040/IJPSR.0975-8232.5(12).5163-69
  65. Mahmood N, Cheishvili D, Arakelian A, et al. Methyl donor S-adenosylmethionine (SAM) supplementation attenuates breast cancer growth, invasion, and metastasis in vivo; therapeutic and chemopreventive applications. Oncotarget. 2017;9(4):5169-83. doi: 10.18632/oncotarget.23704

Copyright (c) 2024 Consilium Medicum

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies