Capecitabine, or Xeloda®, is a prodrug of 5-FU and is currently approved for use in taxane- and anthracycline-resistant breast cancer. However, therapy with capecitabine often results in a painful side effect known as hand-foot syndrome, which is reported to occur in up to 60% of patients and frequently requires dose reduction or cessation of therapy as a result. A breakdown product of 5-FU known as F-BAL is thought to be responsible for this side effect. Eniluracil irreversibly inhibits DPD, the enzyme responsible for the rapid breakdown of 5-FU into metabolites such as F-BAL. In GSK's previous studies of eniluracil in combination with 5-FU, the incidence of hand-foot syndrome was less than 2%. Studies have also shown that the breakdown products of 5-FU, such as F-BAL, can also diminish the effectivenss of 5-FU. Adherex may, therefore, be able to seek approval for eniluracil through either a reduced toxicity profile in comparison to capecitabine or an enhanced efficacy profile, or both.
