5-Fluorouracil (5-FU)
Ð Is a highly toxic drug with a narrow margin of safety. It is
effective against carcinoma
of the colon, rectum, breast, stomach and pancreas, slows or stops
growth of cancer
cells and their spread in the body. Fluorouracil is a fluorinated
pyrimidine. The method of chemical synthesis of Fluorouracil
was described in the US Patent Nos. 2,802,005 and 2,885,396, issued
in 1957 and 1959. The Patents protection for Fluorouracil is expired.
Fluorouracil interferes with the synthesis of DNA
and inhibits the formation of RNA.
Since DNA and RNA are essential for cell
division and grows, the effect of Fluorouracil provokes unbalanced
growth and death of the cell. The effect of DNA and RNA deprivation
are most marked on those cells which grow more rapidly and which
take up Fluorouracil at a more rapid rate, that is, cancer cells.
Fluorouracil is manufactured by Roche Laboratories (a division
of Hoffman-La Roche Inc.) for intravenous administration. Following
the injection, Fluorouracil not only distributes into tumors,
but also into intestinal
mucosa, bone
marrow, liver and other tissues throughout the body. It diffuses
readily across the blood-brain
barrier and distributes into cerebrospinal fluid and brain
tissue. The drug shows an extreme toxicity: severe hematological
toxicity, gastrointestinal
hemorrhage and even death may result from the use of Fluorouracil,
despite meticulous selection of patients and careful adjustment
of dosage.
