While effectively treating cancer, Gleevac can lead to heart failure in some patients, said Dr. Thomas Force, who teaches medicine at Jefferson Medical College of Thomas Jefferson University in Philadelphia.
His study, published Sunday in the online edition of the journal Nature Medicine, was prompted by reports that 10 patients taking Gleevec for chronic myelogenous leukemia developed severe congestive heart failure.
Gleevec, sold under the Glivec in some countries, had worldwide sales of $1.2 billion in the first six months of this year, according to the manufacturer, Novartis Pharmaceuticals Corp.
"Gleevec is a wonderful drug and patients with these diseases need to be on it. It's a lifesaving drug for sure," Force said in a telephone interview.
"This is not a Vioxx situation," Force added, referring to Merck & Co.'s painkiller that was pulled from the market because of heart side effects.
Force said he is trying to call attention to the fact that Gleevec and other similar drugs coming along could have significant effects on the heart and that doctors need to be aware of this and watch for symptoms. These patients can be helped with heart treatment, he said.
Novartis cited the limited data and said further research was needed to better understand the relationship between such studies and their potential impact on monitoring patients who are on the drug.
The company said in a written statement that the prescribing information with the drug includes data on heart problems. In addition, the drug maker said clinical trials and postmarketing safety data have shown that the incidence of heart failures among people taking drug is "extremely rare."
Novartis said Force's work does not change "the positive benefit/risk ratio of Glivec for thousands of patients being treated for cancer and other life-threatening diseases."
Force said the 10 patients with heart failure were taking Gleevec at the University of Texas' M.D. Anderson Cancer Center in Houston and had no heart problems before going on the drug.
He said doctors took baseline measures of the patients' left ventricular heart function and determined that heart failure developed in these patients between two months and 14 months after they began Gleevec.
Dr. Jean-Bernard Durand of M.D. Anderson discussed these cases with Force at a meeting and suggested they try to determine the cause of this problem, Force said.
Gleevec targets three specific proteins, including one called ABL.
In chronic myelogenous leukemia, genes known as ABL and BCR become fused and produce a hybrid BCR-ABL enzyme that is always active. The overactive BCR-ABL, in turn, drives the excessive proliferation of white blood cells that is the hallmark of leukemia.
Using viruses that produced for normal ABL and a Gleevec-resistant mutant in laboratory studies and in mice, the researchers found that Gleevec inhibited the normal enzyme but not the mutant, and the mutant ABL "rescued" heart cells from the toxic effects of Gleevec.
The research was supported by the National Heart, Lung and Blood Institute, the Leukemia and Lymphoma Society, the Finnish Heart Foundation and the Paavo Nurmi Foundation.