Two new drugs recently developed to treat Chronic Myeloid Leukemia, a type of blood cancer, showed significant promise in clinical trials.
A drug known as imatinib mesylate, or Gleevec, is currently the physician’s drug of choice for treating this blood cancer when stem-cell transplant cannot be performed, although some patients may develop resistance to Gleevec if they are in a later stage of the disease.
The American Cancer Society predicts the yearly incidence of Chronic Myeloid Leukemia as 1.6 per 100,000 people every year, with 4,600 estimated cases diagnosed in the United States annually.
Gleevec has often been referred to as a marvel drug due to its ability to halt CML and prolong human lives. Accelerated approval of Gleevec by the Food and Drug Administration allowed Gleevec to go through a rapid development process, becoming available to patients in May 2001. Both researchers and patients hope the new anti-cancer agents will also go through an accelerated federal regulatory process so treatment is available soon.
The new Bristol Myers-Squibb drug BMS-354825 and Novartis drug AMN107 may pick up where Gleevec leaves off, according to some doctors at this year’s annual American Society of Hematology Meeting.
“Chronic Myeloid Leukemia is a cancer that starts in the bone marrow,” said University of Wisconsin hematology specialist Dr. Mark Juckett, who prescribes Gleevec to many of his CML patients. “The cancer is genetic, caused by the Philadelphia chromosome.”
According to the American Society of Hematology website, the Philadelphia translocation is common to about 95 percent of CML patients because of the switching of DNA on human chromosomes 9 and 22. This “hybrid” gene encodes for the overproduction of white blood cells, or cancer, in the bone marrow. Too many white blood cells can “crowd out” normal blood cells and platelets and can eventually spread to other organs.
Gleevec and the two new drugs work similarly, Juckett said. They inhibit specific tyrosine kinase proteins, which account for the abnormal growth in CML.
The new drugs also inhibit specific proteins hypothesized to play a role in Gleevec resistance, according to a University of Texas M.D. Anderson Cancer Center scientific review.
There are three stages of CML: the chronic, accelerated and blast crisis phases. The American Cancer Society says the last phase often converts into drug-resistant leukemia.
A Bristol-Myers press release detailing results of initial BMS-352825 clinical studies involving patients in all three stages indicated that patients with Philadelphia chromosome positive CML who are resistant to Gleevec experienced promising responses with their new anti-cancer agent. In 36 patients in the early, chronic phase, white blood counts returned to normal in 86 percent of patients. In the more advanced CML patients, blood cell counts improved.
The University of Texas M.D. Anderson Cancer Center has also performed initial testing phases of the Novartis AMN107 drug in patients who were resistant to Gleevec treatment. More than 50 percent of patients with CML or the acute version of the disease have had a positive response to the new agent.
This is a unique situation, Juckett said, adding the clinical trials can barely keep up with the vast amount of research and information scientists know about how to treat CML.
“The two new drugs sound very promising,” UW Pharmacy student Emily Doll said. “I hope they can live up to their expectations.”
