Dasatinib, which already has an established role as a second-line agent for chronic myelogenous leukemia, may actually be more effective as a first-line agent than the current standard, imatinib, according to results of a phase II trial presented at the annual meeting of the American Society of Clinical Oncology.

The current work, which was conducted at the University of Texas M. D. Anderson Cancer Center, was led by Ehab L. Atallah, MD, and is ongoing with 35 patients enrolled.

"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," said Atallah, lead author of the study and a fellow in M. D. Anderson's Department of Leukemia.

Dasatinib 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 front-line therapy with imatinib. Both drugs bind to and block a genetically flawed protein known as BCR-ABL, which causes the disease.

Atallah explained that dasatinib binds to both forms of the protein that drives the disease, BCR-ABL, while imatinib blocks only one form.

"Our hypothesis is that treating with dasatinib first will produce an earlier response, which may translate to a better overall survival," Atallah said. "We haven't proved that here, but these early results are encouraging."

The 35 patients enrolled in the clinical trial between November 2005 and December 2006. Patients received either 100 mg dasatinib once daily or 50 mg twice daily. A total of 34 patients had been in the trial for at least three months when Atallah and researcher Jorge Cortes, MD, professor in the Department of Leukemia, evaluated their data.

Initial data review for 34 patients showed that 77 percent at three months, 92 percent at six months, and 95 percent at one year had complete cytogenetic response.

This rapid response rate compares favorably with historical data on patients at the same center who took imatinib as first-line therapy. Imatinib's complete response rates at six months were 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 complete cytogenetic response.

Dasatinib side effects in the current trial have been manageable and mainly low-grade; 15 patients had to temporarily stop treatment.

The clinical trial is set to enroll 100 patients. The comparison with historical data provides insight into dasatinib's effect, but a randomized clinical trial comparing medications directly would present a more detailed picture.