General
Description & Use
Treatment of superficial pre-malignant and malignant skin lesions.
Fluorouracil (Efudix, 5 FU, 5-FU or f5U) is a pyrimidine analog,
which is used as a drug in the treatment of cancer. It belongs
to the family of drugs called antimetabolites. It is typically
administered with Leucovorin.
Uses
The
chemotherapy agent 5-FU (fluorouracil), which has been in use
against cancer for about 40 years, acts in several ways, but principally
as a thymidylate synthase inhibitor. Interrupting the action of
this enzyme blocks synthesis of the pyrimidine thymidine, which
is a nucleotide required for DNA replication. Thymidylate synthase
methylates deoxyuridine monophoshate (dUMP) into thymidine monophosphate
(dTMP).
Like many anti-cancer drugs, 5-FU's effects are
felt system wide but fall most heavily upon rapidly dividing cells
that make heavy use of their nucleotide synthesis machinery, such
as cancer cells (other parts of the body with rapidly dividing
cells include the cells lining the digestive tract).
Some of its principal use is in colorectal cancer
and pancreatic cancer, in which it has been the established form
of chemotherapy for decades (platinum-containing drugs have been
approved for human use in the US since 1978 are also very well
established).
5-FU is also used in ophthalmic surgery, specifically
to augment trabeculectomy (an operation performed to lower the
intraocular pressure in patients with glaucoma) in patients deemed
to be at high risk for failure. 5-FU acts as an anti-scarring
agent in this regard, since excessive scarring at the trabeculectomy
site is the main cause for failure of the surgery.
Fluorouracil can be used topically (as a cream)
for treating actinic (solar) keratoses and some types of basal
cell carcinomas of the skin. It is often referred to by its trade
names Efudex, Carac or Fluoroplex.
It is a key component in Tegafur-uracil.
Mode of action
As a pyrimidine analogue, it is transformed inside the cell into
different cytotoxic metabolites which are then incorporated into
DNA and RNA, finally inducing cell cycle arrest and apoptosis
by inhibiting the cell's ability to synthesize DNA. It is an S-phase
specific drug and only active during certain cell cycles. In addition
to being incorporated in DNA and RNA, the drug has been shown
to inhibit the activity of the exosome complex, an exoribonuclease
complex of which the activity is essential for cell survival.
Capecitabine is a prodrug that is converted into
5-FU in the tissues. It can be administered orally.
