As frontline treatment, imatinib has increased the 5-year survival rate for CML patients from 50 percent to 90 percent. Imatinib targets the aberrant Bcr-Abl protein, caused by a chromosomal abnormality called the Philadelphia Chromosome, which fuels an overabundance of white blood cells and immature stem cells called blasts that crowd out red blood cells and platelets.
Nilotinib and Dasatinib target a greater variety of genetic variations leading to CML than does imatinib.
Both clinical trials continue to enroll patients. Side effects are being closely monitored and some patients in each trial had their doses reduced or treatment temporarily interrupted to deal with toxicities. "We can't say at this moment that either drug has major problems with side effects," Cortes said.
The trials tap M. D. Anderson's longstanding expertise in all three drugs. M. D. Anderson was a leader in the registration clinical trial that led to approval of imatinib for CML.
"As some of our patients started to develop resistance to imatinib, we started searching for agents to bypass that resistance, working with the pharmaceutical companies to test new agents," says Hagop Kantarjian, M.D., chair of M. D. Anderson's Department of Leukemia.
Kantarjian developed, designed and conducted the clinical trials that led to approval of nilotinib by the FDA last month for patients who can no longer take imatinib.
Moshe Talpaz, M.D., developed, designed and conducted clinical trials that led to approval of dasatinib by the FDA in June 2007 for the same group of patients. Talpaz is now at the University of Michigan.
Cortes is leading research into a third drug, bosutinib, produced by Wyeth Pharmaceuticals, as a second-line therapy for CML. (Please see separate n
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center