CHICAGO - An established second-line drug for chronic myelogenous leukemia has high response rates when given to newly diagnosed patients as their first therapy for the disease, according to early results from a Phase II clinical trial at The University of Texas M. D. Anderson Cancer Center.
"Patients taking dasatinib achieve complete cytogenetic response - absence of the mutated protein that drives this disease - more rapidly than we've observed historically using the current front-line therapy. Side effects are very manageable," says Ehab L. Atallah, M.D., lead author of the study and a fellow in M. D. Anderson's Department of Leukemia. Atallah presented study results at the annual meeting of the American Society of Clinical Oncology in Chicago Saturday June 2nd, 2007. The clinical trial remains in progress with 35 patients enrolled.
Dasatinib, known commercially as Sprycel and produced by Bristol-Myers Squibb, was approved by the U.S. Food and Drug Administration a year ago for use by patients whose disease is unresponsive to or becomes resistant to the front-line therapy imatinib. Both drugs bind to and block a genetically flawed protein known as BCR-ABL, which causes the disease. Atallah explains that dasatinib binds to both forms BCR-ABL while imatinib blocks only one.
"Our hypothesis is that treating with dasatinib first will produce an earlier response, which may translate to a better overall survival," Atallah says. "We haven't proved that here, but these early results are encouraging."
Atallah and colleagues evaluated 35 patients who enrolled in the clinical trial between November 2005 and December 2006. Patients receive either 100 mg of dasatinib once daily or 50 mg twice daily.
Thirty four patients had been on the clinical trial for at least three months when Atallah and lead researcher Jorge Cortes, M.D., professor in the Department of Leukemia, evaluated their data. They found that 77 percent of patients at three months, 92 percent at six months and 95 percent at one year had a complete cytogenetic response.
This rapid response compares favorably to historical data on patients at M. D. Anderson who took imatinib as a first therapy, Atallah noted. Imatinib's complete response rates at six months are 54 percent at 400 mg daily and 85 percent for 800 mg daily. However, at 12 months, 72 percent of patients receiving imatinib 400 mg and 92 percent of those receiving 800 mg had a complete cytogenetic response.
Dasatinib side effects have been manageable and mainly low-grade, with 15 patients having to temporarily stop treatment.
The M. D. Anderson clinical trial is set to enroll 100 patients. The comparison to historical data provides insight into dasatinib's effect, but a randomized clinical trial comparing medications directly would present a more detailed picture.
Imatinib, known commercially as Gleevec and produced by Novartis Pharmaceuticals, was the first drug to target the fusion protein BCR-ABL that causes the disease. Before Gleevec, the median five-year survival rate for CML patients was 50 percent. Researchers reported last year that the five-year survival rate of patients taking imatinib is 95 percent.
About 4,500 people receive a diagnosis of CML in the United States each year, and an estimated 20,500 people are living with the disease, according to the Leukemia & Lymphoma Society.
Co-investigators with Atallah are senior researcher Jorge Cortes, M.D., Hagop Kantarjian, M.D., Susan O'Brien, M.D., and Gautam Borthakur, M.B.B.S., all of the M. D. Anderson Department of Leukemia; Daniel Jones, M.D., Ph.D., of the M. D. Anderson Department of Hematopathology; and Claude Nicaise, M.D., of Bristol-Myers Squib Co.
Bristol-Myers sponsors the clinical trial.
Cortes reports having received research grants from Bristol-Myers Squibb. Kantarjian reports having received lecture fees and research grants from Bristol-Myers Squibb. These arrangements are managed by M. D. Anderson in accordance with its conflict of interest policies.