A small but significant study of the cancer-drug Gleevec shows the drug can be toxic to the heart and can lead to heart failure in some patients, raising a possible stumbling block for a treatment that is remarkably successful at treating leukemia.
Researchers who carried out the study, which was published yesterday by the scientific journal Nature Medicine, recommend patients taking Gleevec be monitored for heart-failure symptoms and that other similar drugs in development be tested in early stage trials for evidence of heart toxicity. If further tests confirm that Gleevec can indeed cause heart problems, it will be a setback for the drug and possibly for other targeted therapies, which are designed to attack only cancerous cells while avoiding tissue damage in the rest of the body.
Unlike chemotherapy, "the idea was that [targeted therapies] would limit collateral damage, when in fact we're finding that other tissues can be affected by this model," Jean-Bernard Durand, a cardiologist at M.D. Anderson Cancer Center in Houston and one of the authors of the Nature Medicine paper, said in an interview.
Herceptin, a targeted and highly effective treatment for breast cancer, has also been linked to heart troubles in some patients, though that risk doesn't appear to have slowed the drug's use.
In a statement, Novartis AG, the maker of Gleevec, said clinical trials and other studies of Gleevec have shown that the incidence of heart failure is "extremely rare." Novartis declined to provide a figure. The company said further investigation would be necessary to understand the possible effect of Nature Medicine's study of Gleevec.
Dr. Durand said some patients with heart failure improved and were able to continue taking Gleevec when they were also given heart medication. About 100,000 patients world-wide take the drug.
The researchers writing in Nature Medicine examined 10 patients who developed severe congestive heart failure while taking Gleevec. They also studied the drug's effects in mice and in cultured cells. Because the study was small and not a controlled clinical trial, the researchers said they had no way of knowing what percentage of Gleevec patients might develop heart troubles.
The scientists recommended a more rigorous trial be carried out to gauge the magnitude of the cardiovascular risk. Thomas Force, a cardiologist at Jefferson Medical College in Philadelphia and another of the authors of the Nature Medicine article, said he didn't believe heart troubles would affect a large percentage of Gleevec patients.
Gleevec has proved highly successful at treating chronic myelogenous leukemia, or CML, and a rare stomach cancer known as GIST. A recent study that followed CML patients treated with Gleevec showed that 89% were still alive after five years, a survival rate that cancer specialists deem remarkable.
Michael Deininger, an oncologist at Oregon Health & Science University in Portland, said he believed the new study would prompt closer monitoring of Gleevec patients for heart troubles. But he said Gleevec's benefits still far outweigh its risks.
George Demetri, an oncologist at Dana-Farber Cancer Institute in Boston, agreed. "The fact that we're dealing with lethal cancers allows for some tolerance of side effects," he said.
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