Gleevec May Cause Serious Heart Damage

Posted by rob on July 23, 2006 under Uncategorized | 3 Comments to Read

By Maggie Fox, Health and Science Correspondent 26 minutes ago

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 on Sunday.

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.

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 percent 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.

WATCHING PATIENTS

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.

Novartis said the cases of heart failure in Gleevec patients were extremely rare and said those few patients were successfully treated with two drugs that can help heart failure — ACE inhibitors and carvedilol.

“Further study is necessary to better understand the relationship between these preclinical studies and their potential impact on the clinical management of patients taking Glivec,” the company said in a statement.

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

“The drugs are all tyrosine kinase inhibitors, but each tyrosine kinase is different,” Force said. “It’s difficult to predict what tyrosine kinases will have protective roles in the heart and inhibition of them will be toxic.”

(With additional reporting by Ben Hirschler in London)

Copyright © 2006 Reuters Limited.

Quantification of change in phosphorylation of BCR-ABL kinase and its substrates in response to Imatinib treatment in human chronic myelogenous leukemia cells.

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Quantification of change in phosphorylation of BCR-ABL kinase and its substrates in response to Imatinib treatment in human chronic myelogenous leukemia cells.

Reversible Peripartum Cardiomyopathy in a Patient with Prior Exposure to Interferon.

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Reversible Peripartum Cardiomyopathy in a Patient with Prior Exposure to Interferon.

Gene expression signatures associated with the resistance to imatinib.

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Gene expression signatures associated with the resistance to imatinib.

Glucosamine sulfate-induced apoptosis in chronic myelogenous leukemia K562 cells is associated with translocation of cathepsin D and downregulation of Bcl-xL.

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Glucosamine sulfate-induced apoptosis in chronic myelogenous leukemia K562 cells is associated with translocation of cathepsin D and downregulation of Bcl-xL.

Myeloperoxidase-Catalyzed Metabolism of Etoposide to Its Quinone and Glutathione Adduct Forms in HL60 Cells.

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Myeloperoxidase-Catalyzed Metabolism of Etoposide to Its Quinone and Glutathione Adduct Forms in HL60 Cells.

Successful outcome of pregnancy in a patient with chronic myelogenous leukemia exposed to imatinib during the first trimester.

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Successful outcome of pregnancy in a patient with chronic myelogenous leukemia exposed to imatinib during the first trimester.

Intermittent dosage of imatinib mesylate in CML patients with a history of significant hematologic toxicity after standard dosing.

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Intermittent dosage of imatinib mesylate in CML patients with a history of significant hematologic toxicity after standard dosing.

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