Magazine article Drug Topics

Dasatinib Added to Guidelines for CML

Magazine article Drug Topics

Dasatinib Added to Guidelines for CML

Article excerpt

Dasatinib (Sprycel, BristolMyers Squibb) is a new tyrosine kinase inhibitor for chronic myelogenous leukemia (CML). The Food & Drug Administration approved the drug in June, and now the National Comprehensive Cancer Network (NCCN) has added dasatinib to its CML guidelines.

Dasatinib is indicated for treatment of CML in patients for whom imatinib (Gleevec, Novartis) is ineffective or intolerable. In this population, dasatinib has produced complete cytogenetic response in 33% of patients by the six-month point during clinical studies. "So, we know dasatinib works when imatinib fails," said Susan O'Brien, M.D., professor of medicine in the leukemia department at the University of Texas M. D. Anderson Cancer Center and chair of the CML guidelines panel for NCCN. Although not all patients respond to dasatinib, a significant number do, so NCCN has concluded that dasatinib is now the go-to agent for patients not tolerating or responding to imatinib.

Although imatinib is effective in most CML patients, not all respond adequately. "At any given timepoint, there may be 20% to 30%, of patients qualifying for a switch to dasatinib," said O'Brien. To have two new, effective, and tolerable drugs for CML when five years ago there was little hope is "really revolutionary," she said. "Not only are response rates better, but the difference in tolerability [compared with interferon] is like night and day."

Imatinib was the first tyrosine kinase inhibitor to receive FDA approval for CML. Prior to imatinib, interferon was the drug of choice for CML, said O'Brien. There are several problems with interferon, however. Interferon is injectable and is associated with significant toxicity. More important, only 20% to 50% of patients achieve a cytogenetic response with the drug, and a complete cytogenetic response occurs with even lower frequency, at about 20%. "With Gleevec, it's more like 80% complete cytogenetic response," she said.

Imatinib and dasatinib are oral tablets, so they are easier to administer, and they are both much better tolerated and more effective than interferon. For these reasons, interferon has been removed from most sections of the NCCN CML guidelines.

While imatinib and dasatinib now appear to reign supreme in CML chemotherapy, resistance could potentially topple them from their thrones. According to O'Brien, resistance was a big concern when imatinib was first approved. That is the risk associated with targeted therapies, she explained. …

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