5-fluorouracil: Difference between revisions

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'''5-fluorouracil''' is an antimetabolite fluoropyrimidine analog of the nucleoside pyrimidine, used as an [[antineoplastic agent]] but also as an immunomodulator in [[dermatology]].  
'''5-fluorouracil''' is an antimetabolite fluoropyrimidine analog of the nucleoside pyrimidine, used as an antineoplastic agent]] but also as an immunomodulator in dermatology]].  
==Mechanisms of Action==
==Mechanisms of Action==
Fluorouracil and its metabolites possess a number of different mechanisms of action. In vivo, fluoruracil is converted to the active metabolite 5-fluoroxyuridine monophosphate (F-UMP); replacing uracil, F-UMP incorporates into [[RNA]] and inhibits RNA processing, thereby inhibiting cell growth. Another active metabolite, 5-5-fluoro-2'-deoxyuridine-5'-O-monophosphate (F-dUMP), inhibits [[thymidylate synthase]], resulting in the depletion of [[thymidine triphosphate]] (TTP), one of the four nucleotide triphosphates used in the ''in vivo'' synthesis of [[DNA]]. Other fluorouracil metabolites incorporate into both RNA and DNA; incorporation into RNA results in major effects on both RNA processing and functions. <ref>{{citation
Fluorouracil and its metabolites possess a number of different mechanisms of action. In vivo, fluoruracil is converted to the active metabolite 5-fluoroxyuridine monophosphate (F-UMP); replacing uracil, F-UMP incorporates into RNA]] and inhibits RNA processing, thereby inhibiting cell growth. Another active metabolite, 5-5-fluoro-2'-deoxyuridine-5'-O-monophosphate (F-dUMP), inhibits thymidylate synthase]], resulting in the depletion of thymidine triphosphate]] (TTP), one of the four nucleotide triphosphates used in the ''in vivo'' synthesis of DNA]]. Other fluorouracil metabolites incorporate into both RNA and DNA; incorporation into RNA results in major effects on both RNA processing and functions. <ref>{{citation
  | url = http://www.cancer.gov/drugdictionary/?CdrID=43130
  | url = http://www.cancer.gov/drugdictionary/?CdrID=43130
  | title = fluorouracil
  | title = fluorouracil
  | journal = Drug Dictionary, [[National Cancer Institute]]}}</ref>
  | journal = Drug Dictionary, National Cancer Institute]]}}</ref>
==Dermatology==
==Dermatology==
It is used topically for [[actinic keratosis]]<ref>{{citation
It is used topically for actinic keratosis]]<ref>{{citation
  | title = Actinic Keratosis
  | title = Actinic Keratosis
  | author = James M Spencer & Michelle Henry
  | author = James M Spencer & Michelle Henry
Line 13: Line 13:
  | journal = Medscape  
  | journal = Medscape  
  | url = http://emedicine.medscape.com/article/1099775-overview
  | url = http://emedicine.medscape.com/article/1099775-overview
}}</ref> and superficial [[basal cell carcinoma]]; these indications are approved by the [[Food and Drug Administration]]. Other applications include [[actinic gheilitis]], [[carcinoma in situ]] of the [[glans penis]], [[oral leukoplakia]] and [[radiodermatitis]].
}}</ref> and superficial basal cell carcinoma]]; these indications are approved by the Food and Drug Administration]]. Other applications include actinic gheilitis]], carcinoma in situ]] of the glans penis]], oral leukoplakia]] and radiodermatitis]].
==Oncology==
==Oncology==
Approved parenteral indications are [[colorectal cancer]], localized and metastatic [[gastric cancer]], metastatic [[breast carcinoma]], and [[pancreatic carcinoma]].  Additional uses include malignancy of the [[biliary tract]], localized [[breast carcinoma]], localized tumor of the anus, [[carcinoid syndrome]], [[bladder cancer]] malignancy, malignancy [[esophageal cancer]], [[head and neck tumor]], [[neuroendocrine carcinoma]]<ref>{{citation
Approved parenteral indications are colorectal cancer]], localized and metastatic gastric cancer]], metastatic breast carcinoma]], and pancreatic carcinoma]].  Additional uses include malignancy of the biliary tract]], localized breast carcinoma]], localized tumor of the anus, carcinoid syndrome]], bladder cancer]] malignancy, malignancy esophageal cancer]], head and neck tumor]], neuroendocrine carcinoma]]<ref>{{citation
  | title = Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network
  | title = Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network
  | author = Maria P Brizzi ''et al.''
  | author = Maria P Brizzi ''et al.''
  | journal = BMC Cancer | year = 2009|volume =9| page =388|doi=10.1186/1471-2407-9-388
  | journal = BMC Cancer | year = 2009|volume =9| page =388|doi=10.1186/1471-2407-9-388
  | url = http://www.biomedcentral.com/1471-2407/9/388
  | url = http://www.biomedcentral.com/1471-2407/9/388
}}</ref> and [[bladder cancer]].
}}</ref> and bladder cancer]].


It is often used in combined chemotherapy regimens, and also in concert with [[radiotherapy]].
It is often used in combined chemotherapy regimens, and also in concert with radiotherapy]].
==References==
==References==
{{reflist|2}}
{{reflist|2}}

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5-fluorouracil is an antimetabolite fluoropyrimidine analog of the nucleoside pyrimidine, used as an antineoplastic agent]] but also as an immunomodulator in dermatology]].

Mechanisms of Action

Fluorouracil and its metabolites possess a number of different mechanisms of action. In vivo, fluoruracil is converted to the active metabolite 5-fluoroxyuridine monophosphate (F-UMP); replacing uracil, F-UMP incorporates into RNA]] and inhibits RNA processing, thereby inhibiting cell growth. Another active metabolite, 5-5-fluoro-2'-deoxyuridine-5'-O-monophosphate (F-dUMP), inhibits thymidylate synthase]], resulting in the depletion of thymidine triphosphate]] (TTP), one of the four nucleotide triphosphates used in the in vivo synthesis of DNA]]. Other fluorouracil metabolites incorporate into both RNA and DNA; incorporation into RNA results in major effects on both RNA processing and functions. [1]

Dermatology

It is used topically for actinic keratosis]][2] and superficial basal cell carcinoma]]; these indications are approved by the Food and Drug Administration]]. Other applications include actinic gheilitis]], carcinoma in situ]] of the glans penis]], oral leukoplakia]] and radiodermatitis]].

Oncology

Approved parenteral indications are colorectal cancer]], localized and metastatic gastric cancer]], metastatic breast carcinoma]], and pancreatic carcinoma]]. Additional uses include malignancy of the biliary tract]], localized breast carcinoma]], localized tumor of the anus, carcinoid syndrome]], bladder cancer]] malignancy, malignancy esophageal cancer]], head and neck tumor]], neuroendocrine carcinoma]][3] and bladder cancer]].

It is often used in combined chemotherapy regimens, and also in concert with radiotherapy]].

References

  1. "fluorouracil", Drug Dictionary, National Cancer Institute]]
  2. James M Spencer & Michelle Henry (23 July 2010), "Actinic Keratosis", Medscape
  3. Maria P Brizzi et al. (2009), "Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network", BMC Cancer 9: 388, DOI:10.1186/1471-2407-9-388