Cancer drug toxic to the heart
Glivec has boosted survival rates for people with chronic myeloid leukemia and extended life expectancy for people with a rare type of stomach tumor. The Thomas Jefferson University study, in online Nature Medicine, said people should be aware of the side effects. Drug-maker Novartis said the incidence of heart failure among patients taking Glivec was "extremely rare".
Glivec is one of a new generation of drugs that work on specific targets within the cancer cell.
The researchers from the Philadelphia university investigated Glivec following reports of 10 chronic myeloid leukemia (CML) patients developing severe congestive heart failure while taking the drug. They conducted tests on mice and human heart cells in culture -- and found in both cases that the drug could cause heart failure. -------------------Rogue enzyme
CML is linked to overactivity of an enzyme called the abelson tyrosine kinase (ABL) protein. This overactivity drives the excessive production of white blood cells associated with the cancer. Glivec counters this by turning the enzyme off.
The problem is that ABL also plays a role in keeping cardiac muscle cells healthy. Therefore, knocking the enzyme out potentially compromises the function of these cells in some patients.
To prove this, the researchers showed that Glivec only caused problems in cells containing normal ABL, and not in those containing a mutant form of the protein already known to be resistant to the drug's effect. Lead researcher Dr. Thomas Force said: "Glivec is a wonderful drug and patients with these diseases need to be on it. We're trying to call attention to the fact that Glivec 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."
The researchers say their findings may also apply to other types of drug in the same class -- known as tyrosine kinase inhibitors.
However, each drug is different, and it is difficult to predict which could cause heart problems. -------------------Many benefits
Novartis said the drug's benefits far outweighed the potential risks.
In said the 10 patients who developed signs of heart failure had responded well to treatment for their symptoms. "All Novartis-sponsored studies with Glivec are monitored for safety, and we are committed to conducting further clinical research to ensure safe and effective use of the drug in all patients."
Dr. Laura-Jane Armstrong, of the charity Cancer Research UK, said Glivec saved many lives a year. "It is worth noting that other cancer drugs, including targeted therapies such as Herceptin, also carry some risk of heart problems, but they are still used, as the benefits of treating the cancer far outweigh the heart risks."
Glivec has been shown to extend life expectancy for people with gastrointestinal stromal tumors (GIST).