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New Interest Shown In Flavopiridol...
Back in the 1980s, scientists became excited when tests in animals showed flavopiridol to be a potent cancer-fighter. But when they gave it to humans, the drug proved almost worthless. Just another dead-end
Now researchers at The Ohio State University Comprehensive Cancer Center in Columbus have discovered flavopiridol becomes bound to certain proteins in human blood much more than in animal blood.
These proteins, called serum proteins, tied up much of the available drug, leaving less in the bloodstream to kill cancer cells.
“The researchers had assumed that the drug levels in humans were adequate,” said Thomas Lin, M.D., a member of the OSU's experimental therapeutics program. “But patients were not getting enough of the drug.” In animals, the binding of flavopiridol to the proteins leaves about 60 percent of the drug free to do its job. In humans, however, normal binding leaves only 5-8 percent of the chemotherapy available.
This observation, made initially by Ohio State cancer researchers John Byrd, M.D., and Michael Grever, M.D., led them to devise a new dosing schedule for the drug to increase its anti-tumor activity. The new schedule increased the drug’s blood level enough to kill cancer cells in humans.
In a recent trial many of the patients who responded to the drug had advanced disease and genetic mutations that made it unlikely they would be helped by standard CLL therapies.
The phase I clinical trial involved 42 patients with CLL whose disease had responded poorly to previous treatments. Each week, the patients received the drug during 30-minute rapid intravenous infusion, followed by a slower four-hour infusion. Patients could receive four such doses every six weeks, up to six times.
“Patients with high-risk chromosomal abnormalities that don’t respond to other therapies are doing very well in this trial,” Dr. Lin said. “This drug has been truly remarkable for some patients who did not have other options left.” Of the 42 patients treated, 19 had a significant reduction in their cancer, and this response lasted more than 12 months on average.
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