Cancer drug Gleevec may damage heart - study

By Staff
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WASHINGTON, July 24 (Reuters) Gleevec, the pill that transformed cancer treatments by offering an easy way to target a difficult type of leukemia, may cause serious heart damage, researchers cautioned.

They found evidence that treatment caused heart failure in 10 patients who took Gleevec, made by Swiss drugmaker Novartis.

Patients should not stop taking the drug, known generically as imatinib, but should be watched closely for heart damage, the team at Jefferson Medical College in Philadelphia, Tufts University School of Medicine in Boston, University of Texas and elsewhere said yesterday.

Other drugs in the same class, tyrosine kinase inhibitors, may also damage the heart, the researchers report in the August issue of the journal Nature Medicine.

''Gleevec is a wonderful drug and patients with these diseases need to be on it,'' Thomas Force, who led the study, said in a statement.

''We're trying to call attention to the fact that Gleevec and other similar drugs coming along could have significant side effects on the heart and clinicians need to be aware of this. It's a potential problem because the number of targeted agents is growing rapidly.'' When Gleevec hit the market in 2001, it made headlines because it stopped a difficult type of cancer, chronic myelogenous leukemia or CML, in most patients. Studies show it keeps anywhere between 80 and 90 per cent of CML patients cancer-free for at least five years.

Usually half of the 4,600 new CML patients diagnosed each year die.

Gleevec, sold in Europe as Glivec, is also approved for gastrointestinal stromal tumors or GIST, a rare type of stomach cancer.

It stops the activity of a protein called Bcr-Abl, which causes the out-of-control behavior of white blood cells in CML.

'BIG SURPRISE' Force's team studied the 10 human patients, who developed heart failure while taking Gleevec at M D Anderson Cancer Center in Houston. They then tested the drug in lab dishes and in mice. It appears to be toxic to cardiac cells, they said.

Mice treated with Gleevec developed left ventricular dysfunction, one of the key symptoms of heart failure in which the heart fails to pump out blood completely.

Patients taking Gleevec should be followed closely for symptoms of heart trouble, Force's team advised.

''While the cancer is treated effectively, there will be some percentage of patients who could experience significant left ventricular dysfunction and even heart failure from this,'' Force said in a statement.

Heart failure is a serious and chronic condition that itself kills up to half of patients withing five years.

Drug companies are working on several ''second-generation'' Gleevec-type drugs, and they could also cause the problem, Force said.

''This finding is a big surprise and there may be a lot more of these,'' Force said. ''The drugs are all tyrosine kinase inhibitors, but each tyrosine kinase is different. It's difficult to predict what tyrosine kinases will have protective roles in the heart and inhibition of them will be toxic.'' Jefferson, M D Anderson, the Cleveland Clinic and other cancer centers now plan to start keeping track of patients taking new tyrosine kinase inhibitors. ''As these drugs come out, we can more easily collect data on larger numbers of patients as they take the drugs to get an idea of the incidence of heart problems,'' Force said.

A spokesman at Novartis said the company was preparing a comment.

REUTERS SRS KN0916

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