|Main uses||Gastrointestinal adenocarcinoma, liver cancer, colorectal cancer|
|Side effects||Bone marrow suppression, tiredness, headache, dizziness, trouble sleeping, numbness, abdominal pain, constipation, diarrhea, heart burn, nausea, mouth inflammation, rash|
|Chemical and physical data|
|Molar mass||246.194 g·mol−1|
|3D model (JSmol)|
|Melting point||150.5 °C (302.9 °F)|
Floxuridine is a medication used to treat liver cancer and gastrointestinal adenocarcinoma or colorectal cancer that has spread to the liver. It is given by gradual injection into an artery supplying the cancer.
Common side effects include bone marrow suppression, tiredness, headache, dizziness, trouble sleeping, numbness, abdominal pain, constipation, diarrhea, heart burn, nausea, mouth inflammation, and rash. Other side effects may include liver problems. Due to the severity of side effects people are generally admitted to hospital during initial treatment. It is an antimetabolite, specifically a pyrimidine analog.
Floxuridine was approved for medical use in the United States in 1970. It is available as a generic medication. In the United States 500 mg did costs about 130 USD; though the only manufacturer stopped making the medication in 2019.
It may be given at doses of 0.1 to 0.6 mg/kg/day.
Side effects include:
The following occur in more than 30% of people
- Low blood counts. Your white and red blood cells and platelets may temporarily decrease. This can put you at increased risk for infection, anemia and/or bleeding.
- Mouth sores
- Diarrhea (may be severe)
The following occur in about 10–29% of people
- Poor appetite
- Nausea and vomiting
- Hair loss
- Elevated liver enzymes (temporary increase in alkaline phosphatase, lactate dehydrogenase, transaminase, and bilirubin). This is seen more with the intra-arterial infusion directly into the liver.
- Hand-foot syndrome (Palmar-plantar erythrodysesthesia or PPE) -skin rash, swelling, redness, pain and/or peeling of the skin on the palms of hands and soles of feet
- Stomach ulcers (This is seen more with the intra-arterial infusion).
- Fever of 100.4 °F (38 °C) or higher, chills (possible signs of infection).
- Diarrhea (2 episodes in a 24-hour period)
- Nausea (interferes with ability to eat and unrelieved with prescribed medication)
- Vomiting (vomiting more than 4–5 times in a 24-hour period)
- Mouth sores (painful redness, swelling or ulcers)
- Unusual bleeding or bruising
- Black or tarry stools, or blood in your stools
- Blood in the urine
- Yellowing of the skin or eyes
- Tingling or burning, redness, swelling of the palms of the hands or soles of feet
- Fertility for both men and women may be affected by floxuridine.
Floxuridine primarily works by stopping the growth of newly born cells. The drug essentially stops DNA from forming in new and rapidly developing cells, which is a sign of a cancerous cell. Therefore, the floxuridine kills the cancerous cells. For colorectal cancer and hepatic metastases, an average adult should be given an Intra-arterial dosage of 0.1–0.6 mg/kg/day as a continuous infusion, continued until intolerable toxicity is reached (white blood cell count <3,500/mm^3 or platelet count <100,000/mm^3). Lethal dosages for other species are below. LD50 is the lethal dose at which half of organisms exposed to the drug die.
|Species||LD50 (mg/kg +/- SE)|
|Mouse||880 +/- 51|
|Rat||670 +/- 73|
|Rabbit||94 +/- 19.6|
|Dog||157 +/- 46|
Floxuridine is a pyrimidine analog that acts as an inhibitor of the S-phase of cell division. This selectively kills rapidly dividing cells. Antimetabolites masquerade as pyrimidine-like molecules which prevents normal pyrimidines from being incorporated into DNA during the S phase of the cell cycle. Fluorouracil (the end-product of catabolism of floxuridine) blocks an enzyme which converts cytosine nucleosides into the deoxy derivative. In addition, DNA synthesis is further inhibited because fluoruracil blocks the incorporation of the thymidine nucleotide into the DNA strand.
Mechanism of action
Floxuridine is rapidly catabolized to 5-fluorouracil, which is the active form of the drug. The primary effect is interference with DNA synthesis and to a lesser extent, inhibition of RNA formation through the drug's incorporation into RNA, thus leading to the production of fraudulent RNA. Fluorouracil also inhibits uracil riboside phosphorylase, which prevents the utilization of preformed uracil in RNA synthesis. As well, the monophosphate of floxuridine, 5-fluoro-2'-deoxyuridine-5'-phosphate (FUDR-MP) inhibits the enzyme thymidylate synthetase. This leads to the inhibition of methylation of deoxyuridylic acid to thymidylic acid, thus interfering with DNA synthesis.
The drug is excreted intact and as urea, fluorouracil, α-fluoro-β-ureidopropionic acid, dihydrofluorouracil, α-fluoro-β-guanidopropionic acid and α-fluoro-β-alanine in the urine; it is also expired as respiratory carbon dioxide.
Floxuridine first gained FDA approval in December 1970 under the brand name FUDR. The drug was initially marketed by Roche, which also did a lot of the initial work on 5-fluorouracil. The National Cancer Institute was an early developer of the drug. Roche sold its FUDR product line in 2001 to F H Faulding, which became Mayne Pharma.
Society and culture
Synonyms for floxuridine include:
Apart from its use in chemotherapy, floxuridine is also used in aging research employing a C. elegans model, namely to stop growth and to prevent reproduction. The latter is brought about by treatment of larvae close to maturity with low doses of floxuridine that, even though allowing normal maturation, causes reproducing individuals to lay eggs that are unable to hatch. This limits the population to a single generation allowing quantification of aging processes and measurement of longevity. It has, however, been indicated that floxuridin exposure by itself increases life expectancy potentially leading to flawed data in respective studies.
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