The study led by Jorge Cortes, M.D., professor in the University of Texas M. D. Anderson Cancer Center revealed that the drugs Dasatinib and Nilotinib, currently approved for use as a second line therapy for chronic myelogenous leukemia have shown promise as a frontline therapy for newly diagnosed patients in two clinical trials.
The results were declared in report at the 49th annual meeting of the American Society of Hematology.
In both the trials, after one year on either drug, all the patients had a complete cytogenetic response (absence of the aberrant chromosome that causes the disease).
Almost 90 pct reach complete cytogenetic response as early as 6 months.
"These are early results but certainly encouraging so far in both cases," said Dr. Cortes.
Patients in both trials had been in the chronic or initial phase, of CML and had not received prior therapy for their disease.
The two medications are dasatinib, the Bristol-Myers Squibb drug known as Sprycel(r), and nilotinib, the Novartis drug known as Tasigna(r).
Both the drugs have been approved by the U.S. Food and Drug Administration for use in CML patients whose disease becomes resistant to the frontline therapy imatinib, also a Novartis drug known as Gleevec(r), or who become intolerant to the drug.
Cortes and colleagues compared the two medications at 3, 6 and 12 months with historical data from patients who took either 400 mg or 800 mg daily of Gleevec.
For dasatinib, at three months 26 of 33 patients (79 pct) achieved complete cytogenetic response. At six months 30 of 32 (94 pct) and at 12 months all 24 evaluable patients were at a complete cytogenetic response.
For nilotinib, at three months 21 of 22 patients (95 pct) achieved complete cytogenetic response with all 13 evaluable patients at six months and all 11 at 12 months reaching complete cytogenetic response.
Historical complete cytogenetic responses for low-dose imatinib were 37 pct at three months, 54 pct at six months and 65 pct at a year. For high-dose imatinib the historical response rates were 62 pct, 82 pct and 86 pct.
Imatinib, in its role as frontline treatment, had increased the 5-year survival rate for CML patients from 50 pct to 90 pct.
Imatinib targets the aberrant Bcr-Abl protein, resulted by a chromosomal abnormality called the Philadelphia Chromosome, which triggers an accumulation of white blood cells and immature stem cells called blasts that crowd out red blood cells and platelets.
As compared to imatinib, Nilotinib and Dasatinib target a greater variety of genetic variations leading to CML.
Patients kept enrolling in both the clinical trials. And the researchers closely monitored the side effects 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," said Cortes.
These trials came as result of 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," said 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 could 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.
A research is also led by Cortes, into a third drug, bosutinib, produced by Wyeth Pharmaceuticals, as a second-line therapy for CML.
"We now have enough tools to allow the vast majority of CML patients to live a normal life," said Kantarjian.
He added: "And we are always searching for better alternatives."
All mutations that cause CML are successfully being targeted, except for one, known as the T3151 variant.
"We're looking at other agents to tackle that one," said Kantarjian.