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Glivec's Side effects?


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#1    frogfish

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Posted 26 July 2006 - 02:49 AM

Cancer drug 'toxic to the heart'  

Glivec is an effective leukaemia treatment
A widely hailed cancer drug can damage cardiac tissue and may lead to heart failure, US researchers say.
Glivec has boosted survival rates for people with chronic myeloid leukaemia and extended life expectancy for people with a rare type of stomach tumour.

The Thomas Jefferson University study, in online Nature Medicine, said people should be aware of the side effects.

Drug-maker Novartis said the instances of heart failure among patients taking Glivec were "extremely rare".

Glivec is one of a new generation of drugs that work on specific targets within the cancer cell.

  We are committed to conducting further clinical research to ensure safe and effective use of the drug in all patients

Novartis

The researchers from the Philadelphia university investigated Glivec following reports of 10 chronic myeloid leukaemia (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.

  Other cancer drugs.. carry some risk of heart problems, but they are still used, as the benefits of treating the cancer far outweigh the heart risks

Dr Laura-Jane Armstrong
Cancer Research UK

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."

Ellen Mason, of the British Heart Foundation, said: "Better treatments mean that more people are surviving cancer in the UK, which is wonderful news for many families.

"However, a consequence of being able to treat increased numbers of people with cancer successfully is that we may see more reporting of side effects in survivors."

Glivec has been shown to extend life expectancy for people with gastrointestinal stromal tumours (GIST).

Link
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Glivec should still be taken...It was proven in a study where 400 patients with CML took Glivec. 70% had a decrease in tumors, and sometimes total cure. The current treatement at the time only had 30%. Glivec targets the Philadelphia chromosome, a translocation in CML between 9 and 22...ABL is placed downstream of the promoter BCR, which turns ABL on. In cDNA microarrays, expression of ABL is very high. Glivec targets ABL and downregulates it...

A pretty novel idea. The guy can possibly get a Nobel Prize for Glivec.

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