Abstract
5-Fluorouracil (5-FU) is a mainstay for treating colorectal cancer, alone or more
frequently as part of combination therapies. However, its efficacy/toxicity balance
is often limited by the occurrence of severe toxicities, showing in about 15%-20%
of patients. Several clinical reports have shown the deleterious effect of dihydropyrimidine
dehydrogenase (DPD) genetic polymorphism, a condition that reduces the liver detoxification
step of standard dosages of 5-FU, in patients undergoing fluoropyrimidine-based therapy.
Admittedly, DPD deficiency accounts for 50%-75% of the severe and sometimes life-threatening
toxicities associated with 5-FU (or oral 5-FU). However, technical consensus on the
best way to identify patients with DPD deficiency before administrating 5-FU is far
from being achieved. Consequently, no regulatory step has been undertaken yet to recommend
DPD testing as part of routine clinical practice for securing the administration of
5-FU. This review covers the limits and achievements of the various strategies proposed
so far for determining DPD status in patients scheduled for 5-FU therapy.
Keywords
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Article info
Publication history
Accepted:
May 26,
2010
Received in revised form:
January 5,
2010
Received:
August 12,
2009
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