ASCO: Dasatinib (Sprycel) Works as First-Line Therapy for Chronic Myelogenous Leukemia

CHICAGO, June 2 -- Almost all patients treated off-label with dasatinib (Sprycel) for chronic myelogenous leukemia (CML) had a complete cytogenetic response within a year of beginning therapy, researchers reported here.

"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 Ehab L. Atallah, M.D., a fellow in oncology at the University of Texas M. D. Anderson Cancer Center, in Houston.

He noted that dasatinib, which is approved for treatment of patients who are unresponsive or resistant to treatment with imatinib (Gleevec), was able to achieve a response in 40% of those difficult to treat patients.

"Our hypothesis was that treating with dasatinib first would produce an earlier response, which might translate to a better overall survival," Dr. Atallah said at the American Society of Clinical Oncology meeting. "We haven't proved that here, but these early results are encouraging."

In the study, Dr. Atallah and colleagues treated 35 patients with CML with dasatinib as a first-line therapy. Patients, who were enrolled from November 2005 through December 2006, received either 100 mg of dasatinib once a day or 50 mg twice daily.

Dose escalation to 140 mg/day or 180 mg/day or dose reduction to 80 to 40 mg a day, based on response and toxicity, was permitted.

In 77% of those patients a complete response was achieved as early as three months; 92% of patients had a complete response at 6 months, and 95% had achieved a complete response at 12 months.

Those rates are slightly better than the six-month 54% complete response for low-dose imatinib treatment (400 mg) observed at M. D. Anderson, Dr. Atallah said. At 800 mg daily, imatinib had an 85% response at six months and a 92% complete cytogenetic response at 12 months. The 12-month response for the 400 mg imatinib dose was 72%.

Dasatinib was approved by the FDA a year ago for use in patients whose disease is unresponsive to or becomes resistant to imatinib.

Both drugs bind to and block a genetically flawed protein known as BCR-ABL, which causes the disease. Dr. Atallah noted that dasatinib binds to both open and closed forms of BCR-ABL, while imatinib binds only to the closed form.

Dasatinib's side effects were manageable and mainly low-grade, with 15 patients having to temporarily stop treatment.

"This study is certainly good news for patients with chronic myelogenous leukemia," commented Mitchell Smith, M.D., Ph.D., director of the lymphoma service at Fox Chase Cancer Center in Philadelphia.

"It's always great for patients to have choices and now we have at least two drugs that appear to work very well in this disease," he said, "and there are even other drugs behind dasatinib that are going to be available in case the front-line drugs don't work or are not tolerated."

But Dr. Smith said it was unlikely that doctors would jump on dasatinib as a first-line drug. "We have a lot of experience with imatinib and we will want to see if dasatinib is effective for as long as imatinib. We have evidence that imatinib is effective at least for five years."

Moreover, even with evidence of dasatinib's efficacy, the durability of the treatment effect is unknown. "We still don't know when-or if-it will be possible to stop treatment," said Dr. Smith. "With imatinib, we know that even after a year of treatment, the disease will return if therapy is ended."