PARIS, France--Biochemical modulators have brightened the prospects
for patients with advanced gastrointestinal cancer, Scott Wadler,
MD, reported at the American Radium Society annual meeting.
New evidence suggests that the use of these modulators in combination
with radiation may require revision of traditional assumptions
regarding radiation sensitizers (see below).
The basic principle of biochemical modulation is that one drug
is used to enhance the action of another, as occurs when fluorouracil
is paired with leucovorin, said Dr. Wadler, of the Albert Einstein
College of Medicine.
The conditions necessary for a successful partnership are that
both drugs must have access to the cellular target, one drug must
augment the effects of the other at that target, and there must
be no compensatory mechanism that would enable the cell to develop
Although the addition of leucovorin to fluorouracil therapy in
patients with advanced colorectal cancer has increased the response
rate to 24%, compared with 10% for fluorouracil alone, median
survival has remained static at 11 months, underscoring the need
for more effective therapies for this disease.
Encouraging results came from a phase II study conducted at Albert
Einstein, and a subsequent ECOG trial, which showed that the combination
of fluorouracil and interferon (IFN)-alpha yielded response rates
of 40% to 60%.