The cancer drug that last month won the government's fastest approval ever is proving ineffective against an advanced form of leukemia, but scientists say they remain buoyed by the drug's otherwise stellar performance.
Gleevec, known scientifically as STI-571 and manufactured by Novartis AG, was deliberately designed to target the precise mechanism that goes awry in chronic myelogenous leukemia, CML. The drug is in the vanguard of new targeted therapies that zero in on a given cancer's biochemical bull's-eye -- the exact cause of the disease -- eschewing the broad-spectrum effects of traditional chemotherapy.
However, scientists reporting Friday in the journal Science say the drug shares a common characteristic of traditional chemotherapy: resistance. It can be repelled by the very cells it is supposed to destroy.
"This is an excellent drug; we're not discrediting the drug," said Dr. Charles L. Sawyers, a hematologist at the University of California, Los Angeles and the study's lead investigator.
In Sawyers' study of 11 patients with advanced CML, all relapsed within three to six months of taking Gleevec. By contrast, patients in earlier phases of the disease have gone into remissions that so far appear to be lasting. No one has taken Gleevec longer than three years, and the issue of Gleevec's resistance may be instructive, medical scientists say.
"This report is asking why they relapsed and what is the molecular basis for the relapse," Sawyers said.
CML is a form of leukemia in which the white blood cells known as granulocytes emerge from the bone marrow immature and bearing a genetic flaw. That defect, known as bcr-abl, forces overproduction of the enzyme tyrosine kinase, which in turn accelerates the production of immature granulocytes. The drug works by blocking tyrosine kinase, driving the cancer into remission.
Sawyers said in CML's most advanced form, blast crisis, which can occur within five years of diagnosis with traditional therapies, patients' cancer cells accumulate far more than the bcr-abl genetic error. In the disease's most advanced phase, numerous genetic aberrations stipple the CML cells.
While Gleevec normally works by inhibiting tyrosine kinase, in blast crisis, tyrosine kinase steps up its activity, hence overwhelming the drug.
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