Fluorouracil (5-FU)
General information
Class/mechanism: Pyrimidine analog, antimetabolite, inhibitor of thymidylate synthase. Metabolized to 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP inhibits DNA synthesis by binding to thymidylate synthase and inhibiting production of thymidylate; FUTP interferes with RNA processing when it is mistakenly incorporated in place of uridine triphosphate (UTP).[1][2].
Route: IV
Extravasation: irritant
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias or the prescribing information.[1]
Patient safety
DPYD intermediate or poor metabolizers: Results in higher adverse reaction risk (severe, life-threatening, or fatal toxicities). No dosage has proven safe in poor metabolizers, and insufficient data are available to recommend a dosage in intermediate metabolizers. Withhold or discontinue in the presence of early-onset or unusually severe toxicity.[3]
EMA has recommended that patients should be tested for the lack of the enzyme dihydropyrimidine dehydrogenase (DPD) before starting cancer treatment with fluorouracil given by injection or infusion (drip) or with the related medicines, capecitabine and tegafur.
References
- Delaunoit T, Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Findlay BP, Thomas SP, Salim M, Schaefer PL, Stella PJ, Green E, Mailliard JA. Mortality associated with daily bolus 5-fluorouracil/leucovorin administered in combination with either irinotecan or oxaliplatin: results from Intergroup Trial N9741. Cancer. 2004 Nov 15;101(10):2170-6. link to original article PubMed
Diseases for which it is established (work in progress)
Diseases for which it is used
- Anal cancer
- Bladder cancer
- Breast cancer
- Carcinoma of unknown primary
- Cervical cancer
- Cholangiocarcinoma
- Colorectal cancer
- Esophageal cancer
- Gallbladder cancer
- Gastric cancer
- Head and neck cancer
- Hepatoblastoma
- Neuroendocrine tumor
- Pancreatic cancer
- Pancreatic NET
- Penile cancer
- Small bowel adenocarcinoma
Diseases for which it was used
Patient drug information
- Fluorouracil (5-FU) Package Insert[4]
- Fluorouracil (5-FU) patient drug information (Chemocare)[5]
- Fluorouracil (5-FU) patient drug information (UpToDate)[6]
History of changes in FDA indication
- 1962-04-25: Initial FDA approval
- Uncertain date: Approved for the treatment of patients with adenocarcinoma of the colon and rectum; adenocarcinoma of the breast; gastric adenocarcinoma; and pancreatic adenocarcinoma. (No supporting studies are cited)
History of changes in EMA indication
- 1977-12-16: EURD
History of changes in PMDA indication
- 2013-12-20: New additional indication and a new dosage for the treatment of unresectable pancreatic cancer.
- 2018-09-21: New indication and a new dosage for the treatment of small intestine cancer.
- 2021-11-25: New indication and a new dosage for the treatment of esophageal cancer.
Also known as
- Code name: Ro-2-9757
- Generic names: 5 Fluorouracil, 5 FU, 5-FU, 5-fluoracilo, 5-fluorouracilo, 5-fluorouracyl, FU
- Brand names:
Synonyms | |||||||
---|---|---|---|---|---|---|---|
Accusite | Actino Hermal | Adrucil | Arumel | Benton | Biofur | Carac | Carebin |
Carzonal | Cinco-FU | Cinkef-U | Curacil | Effcil | Efudex | Efurix | Ezadex |
Fauldfluor | Fivocil | Fivoflu | Flacule | Flonida | Florac | Fluhomer | Fluolex |
Fluoroplex | Fluor-Uracil | Fluoro-Uracile ICN | Fluoro-Uracil ICN | Fluorouracile | Fluorouracilo | Fluorourcil | Fluoruracilo |
Fluoxan | Flurablastin | Flurac | Fluracedyl | Fluracil | Fluril | Fluroblastin | Fluroblastine |
Ftoruracil | Ftouracil | Haemato-FU | Ifacil | Kang Ning | Kecimeton Tatumi | Killit | Lunachol |
Lunapon | Natira U | Neofluor | O Fluor | Oncofu | Onkofluor | Pentafu | Pharmauracil |
Phthoruracil | Phtoruracil | Ribofluor | Rotianin | Satelol | Seco Uracil | Tecflu | Timadin |
Triosules | Uflahex | Ulosagen | Ulup | Uraciflor | Utoral | Vaflu | Vafu |
References
- Drugs
- Intravenous medications
- Topical medications
- Irritant
- Fluoropyrimidines
- Anal cancer medications
- Bladder cancer medications
- Breast cancer medications
- Carcinoma of unknown primary medications
- Cervical cancer medications
- Cholangiocarcinoma medications
- Colon cancer medications
- Colorectal cancer medications
- Esophageal adenocarcinoma medications
- Esophageal cancer medications
- Esophageal squamous cell carcinoma medications
- Gallbladder cancer medications
- Gastric cancer medications
- Head and neck cancer medications
- Hepatoblastoma medications
- Hepatocellular carcinoma medications
- Nasopharyngeal carcinoma medications
- Neuroendocrine tumor medications
- Pancreatic cancer medications
- Pancreatic NET medications
- Penile cancer medications
- Rectal cancer medications
- Small bowel adenocarcinoma medications
- Diffuse large B-cell lymphoma medications (historic)
- Ovarian cancer medications (historic)
- Prostate cancer medications (historic)
- FDA approved in 1962
- EMA approved in 1977
- WHO Essential Cancer Medicine