Dasatinib Effective in Blast-Crisis Chronic Myeloid Leukemia
Adapted from the NCI Cancer Bulletin.Patients who enter the blast-crisis phase of chronic myeloid leukemia (BC-CML), in which 30 percent of the cells in the blood or bone marrow are immature blood cells, typically survive only three to six months. Results from eight months of follow-up of a pair of phase II clinical trials published in the April 15, 2007, issue of Blood show that dasatinib, a new small-molecule inhibitor that has many targets within leukemia cells, can induce lasting hematologic (concerning the blood) and cytogenetic (concerning the chromosomes) responses in patients with BC-CML (see the journal abstract).
Investigators enrolled 42 patients with lymphoid blast crisis (LBC) and 74 patients with myeloid blast crisis (MBC) into two separate but identical trials (see the protocol summaries for CA180-006 and CA180-015). All patients were either resistant to or intolerant of imatinib, a small-molecule inhibitor used in first-line therapy of CML. Patients received a starting dose of 70 mg of dasatinib twice daily, which could be escalated after four weeks. Dose reductions or interruptions were allowed in response to side effects.
Patients received dasatinib until disease progression despite dose escalation, intolerable toxicity, or withdrawal from the study. Among patients with MBC, 32 percent had a major hematologic response at six months of follow-up; this number rose to 34 percent after eight months. Among patients with LBC, 31 percent had a major hematologic response at both six and eight months of follow-up. Twenty-seven percent of MBC patients and 43 percent of LBC patients had a complete cytogenetic response. Only 11 percent of patients with MBC and two percent of patients with LBC had to discontinue therapy because of side effects.
"Our results indicated that dasatinib represents a potentially important new therapeutic option for patients with imatinib-resistant or imatinib-intolerant MBC-CML or LBC-CML and will undoubtedly affect the treatment paradigm for CML," concluded the authors.