Source: Epilepsy Curr  |  Posted 5 years ago

By Charlene Laino

WASHINGTON, D.C. -- April 7, 2006 -- The second-generation tyrosine kinase inhibitor dasatinib (BMS-354825) shows promise for the treatment of patients with chronic myelogenous leukemia (CML) who have developed resistance to imatinib mesylate (Gleevec), suggest the results of several phase 2 studies.

Charles Sawyers, MD, professor of medicine, Division of Hematology-Oncology, University of California in Los Angeles, United States, said there are now 5 phase 2 studies testing the agent in resistant patients.

Imatinib is now considered front-line therapy for newly diagnosed CML. However, it is associated with a significant relapse rate, Dr. Sawyers explained.

Several studies are currently evaluating dasatinib in the treatment of imatinib-resistant CML. Dr. Sawyers presented 6-month data on 4 of these studies on April 3[^]rd[] at the 97[^]th[] Annual Meeting of the American Association for Cancer Research (AACR).

Among the findings:

? In one study of 186 patients with chronic phase CML treated with dasatinib, 90 have had a complete hematologic remission, defined as normalization of blood counts. Additionally, 45 patients have had a major cytologic remission, defined as 35% or fewer Philadelphia chromosome positive cells.

? In a study of 107 patients with accelerated phase CML, 59 had a complete hematologic remission and 31 have had a major cytologic remission.

? In a study of 78 patients with lymphoid blast crisis, 35 had complete hematologic responses and 54 have had a major cytologic remission.

? In a study of 74 patients with myeloid blast disease, 32 had a complete hematologic remission and 30 have had a major cytologic remission.

In the phase 2 trial, 51% to 79% of patients developed Grade 3 and 4 myelosuppression, and 12% to 18% of patients have had pleural effusions.

The fifth phase 2 study, a randomized trial pitting dasatinib against high-dose imatinib in patients with suboptimal responses to standard-dose imatinib, has just completed accrual, Dr. Sawyers said.

[Presentation title: Development of the ABL Kinase Inhibitor Dasatinib (BMS-354825) in Imatinib-Resistant Philadelphia Chromosome Positive Leukemias. Abstract CP-2]