5-FLUOROURACIL: A LITERATURE REVIEW
Abstract
The occurrence of cancer is very vast throughout the world. To try to solve or reduce these impacts, the various therapies have been designed over the years, including medicine. The use of drugs for cell inhibition is an efficient method of tumor cells. However, current treatments also address many adverse effects on cells. In this context, 5-fluorouracil (5-FU), one of the most used antineoplastic agents, is a cheap and efficient compound for solid cancer. Given the wide use of this term, studies have been developed with the objective of evaluating its mechanisms of action and effects. The cytotoxicity of 5-FU is known to be relatively high and some patients have very harmful effects, which makes the treatment must be interrupted. In this way, you adjust your dose order to find a balance between therapeutic benefit and harm. Thus, understanding the mechanisms of action of the FU drug becomes essential for the search for drugs that can help reduce the side effects of this chemotherapeutic agent. Therefore, the main objective of this work is to help understand the mechanisms of action of 5-FU and its adverse effects.
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References
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CAPITAIN, O. et al. The influence of fluorouracil outcome parameters on tolerance and efficacy in patients with advanced colorectal cancer. Pharmacogenomics Journal, v. 8, n. 4, p. 256–267, 2008.
CHIONH, F. et al. Oral versus intravenous fluoropyrimidines for colorectal cancer. Cochrane Database of Systematic Reviews, n. 7, 2017.
CORONADO-CERDA, E. E. et al. In Vivo Chemoprotective Activity of Bovine Dialyzable Leukocyte Extract in Mouse Bone Marrow Cells against Damage Induced by 5-Fluorouracil. Journal of Immunology Research, v. 2016, p. 10, 2016.
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FREEMAN, K. et al. Fluorouracil plasma monitoring: Systematic review and economic evaluation of the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion. Health Technology Assessment, v. 19, n. 91, 2015.
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KIM, H. I.; LIM, H.; MOON, A. Sex differences in cancer: Epidemiology, genetics and therapy. Biomolecules and Therapeutics, v. 26, n. 4, p. 335–342, 2018.
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LAMBERTI, M. et al. 5-Fluorouracil induces apoptosis in rat cardiocytes through intracellular oxidative stress. Journal of Experimental and Clinical Cancer Research, v. 31, n. 1, p. 1, 2012.
LONGLEY, D. B.; HARKIN, D. P.; JOHNSTON, P. G. 5-Fluorouracil: Mechanisms of action and clinical strategies. Nature Reviews Cancer, v. 3, n. 5, p. 330–338, 2003.
MAIA, V. R. et al. Protocolos de Enfermagem: administração de quimioterapia antineoplásica no tratamento de hemopatias malignas. Hemorio. 1° ed. 2010.
MILANO, G. et al. Influence of sex and age on fluorouracil clearance. J. Clin. Oncol., v. 10, p. 1171-1175, 1992.
MIRANDA, J. A. L. et al. Protective effect of cashew gum on 5-fluorouracil-induced intestinal Mucositis. Pharmaceuticals, v. 12, n. 2, p. 1–17, 2019.
MORAWSKA, K. et al. 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer. Oncotarget, v. 9, n. 14, p. 11559–11571, 2018.
RIAHI-CHEBBI, I. et al. The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells. Scientific Reports, v. 9, n. 1, p. 1–20, 2019.
RIUL, S.; AGUILLAR, O. M. Quimioterapia antineoplásica: revisão da literatura. Revista Mineira de Enfermagem, v. 3, n. 1, p. 60–67, 1999.
SAIF, M. W. et al. Pharmacokinetically guided dose adjustment of 5-fluorouracil: A rational approach to improving therapeutic outcomes. Journal of the National Cancer Institute, v. 101, n. 22, p. 1543–1552, 2009.
SCHEIN, C. F. et al. Efeitos colaterais da quimioterapia em pacientes oncológicos hospitalizados. Disc. Scientia. Série Ciencias da Saúde, v. 7, n. 1, p. 101–7, 2006.
SCHOEDEL, K. B. et al. The bulk of the hematopoietic stem cell population is dispensable for murine steady-state and stress hematopoiesis. Blood, v. 128, n. 19, p. 2285–2296, 2016.
SCHUETZ, J. D.; WALLACE, H. J. 5-Fluorouracil Incorporation into DNA of CF-1 Mouse Bone Marrow Cells as a Possible Mechanism of Toxicity. Cancer Research, v. 44, n. 4, p. 1358–1363, 1984.
SHAPIRO, M. S. et al. 5-Fluorouracil toxicity to the ocular surface epithelium. Investigative Ophthalmology and Visual Science, v. 26, n. 4, p. 580–583, 1985.
SHARMA, V.; GUPTA, S. K.; VERMA, M. Dihydropyrimidine dehydrogenase in the metabolism of the anticancer drugs. Cancer Chemotherapy and Pharmacology, 2019.
STINTZING, S. et al. Correlation of capecitabine-induced skin toxicity with treatment efficacy in patients with metastatic colorectal cancer: Results from the German AIO KRK-0104 trial. British Journal of Cancer, v. 105, n. 2, p. 206–211, 2011.
SUN, Y.; HUA, R. Ocular surface squamous neoplasia: Angiographic characteristics and response to subconjunctival/ perilesional 5-fluorouracil injections. Drug Design, Development and Therapy, v. 13, p. 1323–1334, 2019.
THALAMBEDU, N.; KHAN, Y. Fluorouracil (5-FU)-induced Cardiomyopathy. Cureus, v. 11, n. 7, p. 1–7, 2019.
UNTURA, L. P.; REZENDE, L. F. Cognitive function in patients undergoing chemotherapy: a systematic review. Rev. bras. cancerol, v. 58, n. 2, p. 257–265, 2012.
WELBAT, J. U. et al. Neuroprotective properties of asiatic acid against 5-fluorouracil chemotherapy in the hippocampus in an adult rat model. Nutrients, v. 10, n. 8, 2018.
WERBEL, T.; COHEN, P. R. Topical Application of 5-Fluorouracil Associated with Distant Seborrheic Dermatitis-like Eruption : Case Report and Review of Seborrheic Dermatitis Cutaneous Reactions after Systemic or Topical Treatment with 5-Fluorouracil. Dermatology and Therapy, v. 8, n. 3, p. 495–501, 2018.
WIGLE, T. J. et al. DPYD and fluorouracil-based chemotherapy: Mini review and case report. Pharmaceutics, v. 11, n. 5, p. 1–17, 2019.
WORLD HEALTH ORGANIZATION. Estimated cancer incidence, mortality and prevalence worldwide in 2018. Lion: IARC, 2018. Disponível em:. Acesso em: 39 set. 2019.
AMSTUTZ, U.; FROEHLICH, T. K.; LARGIADR, C. R. Dihydropyrimidine dehydrogenase gene as a major predictor of severe 5-fluorouracil toxicity. Pharmacogenomics, v. 12, n. 9, p. 1321–1336, 2011.
ARIAS, J. L. Novel strategies to improve the anticancer action of 5-fluorouracil by using drug delivery systems. Molecules, v. 13, n. 10, p. 2340–2369, 2008.
BOUCHERVILLE, Q. C. Fluorouracil injection USP. Monografia, 2012.
BRANDÃO, H. N. et al. Química e farmacologia de quimioterápicos antineoplásicos derivados de plantas. Recherche Aerospatiale (English Edition), v. 33, n. 1, p. 1–15, 2010.
BRASIL, Ministério da Saúde. Abc Do Câncer. Rio de Janeiro: Instituto Nacional de Câncer, 2011.
BRASIL, Ministério da Saúde. Ações de enfermagem para o controle do câncer. 3° ed. cap.6 Rio de Janeiro, 2008.
BRASIL, Ministério da Saúde. A situação do câncer no Brasil. INCA, Rio de Janeiro, 2006.
BRASIL, Ministério da Saúde. Estimativa | 2014 Incidência de Câncer no Brasil. Rio de Janeiro, 2014.
BUKHARI, D. A.; ALESSA, S. K.; BEHEIRI, S. I. Corneal epithelial hyperplasia after 5-fluorouracil injection. Case Reports in Ophthalmology, v. 9, n. 1, p. 254–256, 2018.
CAPITAIN, O. et al. The influence of fluorouracil outcome parameters on tolerance and efficacy in patients with advanced colorectal cancer. Pharmacogenomics Journal, v. 8, n. 4, p. 256–267, 2008.
CHIONH, F. et al. Oral versus intravenous fluoropyrimidines for colorectal cancer. Cochrane Database of Systematic Reviews, n. 7, 2017.
CORONADO-CERDA, E. E. et al. In Vivo Chemoprotective Activity of Bovine Dialyzable Leukocyte Extract in Mouse Bone Marrow Cells against Damage Induced by 5-Fluorouracil. Journal of Immunology Research, v. 2016, p. 10, 2016.
DEVITA, V. T.; CHU, E. A history of cancer chemotherapy. Cancer Research, v. 68, n. 21, p. 8643–8653, 2008.
EUROFARMA. Flusan (fluorouracila) - bula para o profissional da saúde, 2015. Disponível em:
FANG, L. et al. Pharmacokinetically guided algorithm of 5-fluorouracil dosing, a reliable strategy of precision chemotherapy for solid tumors: A meta-analysis. Scientific Reports, v. 6, n. January, p. 1–7, 2016.
FREEMAN, K. et al. Fluorouracil plasma monitoring: Systematic review and economic evaluation of the My5-FU assay for guiding dose adjustment in patients receiving fluorouracil chemotherapy by continuous infusion. Health Technology Assessment, v. 19, n. 91, 2015.
GAMELIN, E. et al. Individual fluorouracil dose adjustment based on pharmacokinetic follow-up compared with conventional dosage: Results of a multicenter randomized trial of patients with metastatic colorectal cancer. Journal of Clinical Oncology, v. 26, n. 13, p. 2099–2105, 2008.
GREM, J. L. 5-Fluorouracil: Forty-plus and still ticking. A review of its preclinical and clinical development. Investigational New Drugs, v. 18, n. 4, p. 299–313, 2000.
HARRIS, D. J. Cancer treatment-induced mucositis pain: Strategies for assessment and management. Therapeutics and Clinical Risk Management, v. 2, n. 3, p. 251–258, 2006.
HONG, B. Y. et al. Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis. Microbiome, v.7, n.1, 2019.
INSTITUTO NACIONAL DO CÂNCER. Estimativa 2018: Incidência de Câncer no Brasil. Rio de Janeiro, 2018.
JOAG, M. G. et al. Topical 5-fluorouracil 1% as primary treatment for ocular surface squamous neoplasia Madhura. Ophthalmology, v. 123, n. 7, p. 69–81, 2017.
KIM, H. I.; LIM, H.; MOON, A. Sex differences in cancer: Epidemiology, genetics and therapy. Biomolecules and Therapeutics, v. 26, n. 4, p. 335–342, 2018.
LACERDA, M. A. Quimioterapia e Anestesia. Revista Brasileira de Anestesiologia, v. 51, n. 3, p. 250–270, 2001.
LAMBERTI, M. et al. 5-Fluorouracil induces apoptosis in rat cardiocytes through intracellular oxidative stress. Journal of Experimental and Clinical Cancer Research, v. 31, n. 1, p. 1, 2012.
LONGLEY, D. B.; HARKIN, D. P.; JOHNSTON, P. G. 5-Fluorouracil: Mechanisms of action and clinical strategies. Nature Reviews Cancer, v. 3, n. 5, p. 330–338, 2003.
MAIA, V. R. et al. Protocolos de Enfermagem: administração de quimioterapia antineoplásica no tratamento de hemopatias malignas. Hemorio. 1° ed. 2010.
MILANO, G. et al. Influence of sex and age on fluorouracil clearance. J. Clin. Oncol., v. 10, p. 1171-1175, 1992.
MIRANDA, J. A. L. et al. Protective effect of cashew gum on 5-fluorouracil-induced intestinal Mucositis. Pharmaceuticals, v. 12, n. 2, p. 1–17, 2019.
MORAWSKA, K. et al. 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer. Oncotarget, v. 9, n. 14, p. 11559–11571, 2018.
RIAHI-CHEBBI, I. et al. The Phenolic compound Kaempferol overcomes 5-fluorouracil resistance in human resistant LS174 colon cancer cells. Scientific Reports, v. 9, n. 1, p. 1–20, 2019.
RIUL, S.; AGUILLAR, O. M. Quimioterapia antineoplásica: revisão da literatura. Revista Mineira de Enfermagem, v. 3, n. 1, p. 60–67, 1999.
SAIF, M. W. et al. Pharmacokinetically guided dose adjustment of 5-fluorouracil: A rational approach to improving therapeutic outcomes. Journal of the National Cancer Institute, v. 101, n. 22, p. 1543–1552, 2009.
SCHEIN, C. F. et al. Efeitos colaterais da quimioterapia em pacientes oncológicos hospitalizados. Disc. Scientia. Série Ciencias da Saúde, v. 7, n. 1, p. 101–7, 2006.
SCHOEDEL, K. B. et al. The bulk of the hematopoietic stem cell population is dispensable for murine steady-state and stress hematopoiesis. Blood, v. 128, n. 19, p. 2285–2296, 2016.
SCHUETZ, J. D.; WALLACE, H. J. 5-Fluorouracil Incorporation into DNA of CF-1 Mouse Bone Marrow Cells as a Possible Mechanism of Toxicity. Cancer Research, v. 44, n. 4, p. 1358–1363, 1984.
SHAPIRO, M. S. et al. 5-Fluorouracil toxicity to the ocular surface epithelium. Investigative Ophthalmology and Visual Science, v. 26, n. 4, p. 580–583, 1985.
SHARMA, V.; GUPTA, S. K.; VERMA, M. Dihydropyrimidine dehydrogenase in the metabolism of the anticancer drugs. Cancer Chemotherapy and Pharmacology, 2019.
STINTZING, S. et al. Correlation of capecitabine-induced skin toxicity with treatment efficacy in patients with metastatic colorectal cancer: Results from the German AIO KRK-0104 trial. British Journal of Cancer, v. 105, n. 2, p. 206–211, 2011.
SUN, Y.; HUA, R. Ocular surface squamous neoplasia: Angiographic characteristics and response to subconjunctival/ perilesional 5-fluorouracil injections. Drug Design, Development and Therapy, v. 13, p. 1323–1334, 2019.
THALAMBEDU, N.; KHAN, Y. Fluorouracil (5-FU)-induced Cardiomyopathy. Cureus, v. 11, n. 7, p. 1–7, 2019.
UNTURA, L. P.; REZENDE, L. F. Cognitive function in patients undergoing chemotherapy: a systematic review. Rev. bras. cancerol, v. 58, n. 2, p. 257–265, 2012.
WELBAT, J. U. et al. Neuroprotective properties of asiatic acid against 5-fluorouracil chemotherapy in the hippocampus in an adult rat model. Nutrients, v. 10, n. 8, 2018.
WERBEL, T.; COHEN, P. R. Topical Application of 5-Fluorouracil Associated with Distant Seborrheic Dermatitis-like Eruption : Case Report and Review of Seborrheic Dermatitis Cutaneous Reactions after Systemic or Topical Treatment with 5-Fluorouracil. Dermatology and Therapy, v. 8, n. 3, p. 495–501, 2018.
WIGLE, T. J. et al. DPYD and fluorouracil-based chemotherapy: Mini review and case report. Pharmaceutics, v. 11, n. 5, p. 1–17, 2019.
WORLD HEALTH ORGANIZATION. Estimated cancer incidence, mortality and prevalence worldwide in 2018. Lion: IARC, 2018. Disponível em:
Published
2022-09-05
How to Cite
1.
SILVA MC. 5-FLUOROURACIL: A LITERATURE REVIEW. arqmudi [Internet]. 2022Sep.5 [cited 2025Nov.6];26(2):112-25. Available from: https://periodicos.uem.br/ojs/index.php/ArqMudi/article/view/63239
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Review article in Science, Biology and Biodiversity
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