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Dasatinib's Bleeding Complications Confirmed, Explained: Presented at ASH

By John Gever

ATLANTA, GA -- December 12, 2007 -- Reports of bleeding complications with dasatinib therapy were confirmed and traced to the drug's induction of aspirin-like platelet inhibition, according to studies.

The results were presented in two posters here on December 10 at the 49th American Society of Hematology (ASH) Annual Meeting and Exposition by senior author Jorge Cortes, MD, Professor of Leukemia, M.D. Anderson Cancer Center, Houston, Texas.

"Patients receiving dasatinib should avoid concomitant therapy with agents that may inhibit platelet function," the researchers recommended.

Dasatinib is used to treat chronic-phase chronic myeloid leukemia (CML) in patients with unsuccessful results on imatinib. It is also under study as a first-line treatment for CML.

Several studies of dasatinib have reported bleeding events in numbers not seen with imatinib.

Dr. Cortes's group examined records from two clinical trials of dasatinib involving a total of 138 patients. Both were dose-finding studies, hence patients received a range of doses, from 15 mg/day to 180 mg/day.

The analysis found that 23% of patients experienced bleeding events. "This complication is particularly prevalent among patients with advanced CML receiving [at least] 140 mg," the researchers said.

Of the 37 bleeding episodes seen in the studies, 23 were grade 1 or 2, with the remaining events all grade 3 (requiring transfusion).

These were managed adequately, Dr. Cortes's group said, with dasatinib treatment interruptions lasting a median of 17 days used in about half the cases.

Platelet counts below 30,000/mcL were seen in 43% of cases; the platelet counts were between 30,000 and 100,000/mcL in another 16%.

The findings prompted Dr. Cortes's group to undertake a laboratory study of dasatinib's effect on platelet function in comparison with similar CML drugs (imatinib, nilotinib, and bosutinib). Standard coagulation tests and platelet function analyses were performed on blood samples from a total of 55 patients taking these drugs.

All but two of these patients showed normal results on prothrombin and activated partial thromboplastin time tests.

But platelet function was inhibited with dasatinib "causing an aspirin-like effect," the researchers said. Impaired platelet aggregation was found in samples from 85% of dasatinib patients, significantly more than in patients treated with bosutinib (20%), or nilotinib or imatinib (33% combined) (P <.006).


[Presentation title: Dasatinib-Induced Platelet Dysfunction; Bleeding Diathesis in Patients (pts) With Chronic Myelogenous Leukemia Receiving Dasatinib Therapy. Abstracts 2941 and 2958]

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