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(Drug information on 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 resistance.
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%.