Navigation Links
Another 'smart' cancer drug can have toxic effects on the heart
Date:12/13/2007

Another FDA-approved targeted cancer drug, sunitinib (SutentTM, Pfizer), may be associated with cardiac toxicity, report researchers at Childrens Hospital Boston, Dana-Farber Cancer Institute (Boston), and Thomas Jefferson University (Philadelphia). Their collaborative study, led by Ming Hui Chen, MD, MMSc, a cardiologist at Childrens who specializes in the cardiac health of cancer patients, appears in the December 15 issue of The Lancet, accompanied by an editorial.

Sunitinib is one of several new smart cancer drugs called tyrosine kinase inhibitors that targets specific signaling molecules inside cancer cells that aid cancer spread. Another targeted cancer therapy, imatinib (GleevecTM, Novartis Pharmaceuticals), was reported last year in Nature Medicine to be associated with heart failure in patients with chronic myelogenous leukemia.

Sunitinib was originally thought to be relatively free of cardiac side effects. However, a new retrospective analysis, focused on cardiovascular events, revealed a risk for heart failure, myocardial infarction and hypertension in 75 adult patients with imatinib-resistant, gastrointestinal stromal tumor (GIST) receiving multiple cycles of sunitinib in a phase I/II trial at Dana-Farber.

Of the 75, six (8 percent) developed symptoms consistent with moderate-to-severe congestive heart failure, and two had heart attacks. In all, eight (11 percent) had some kind of cardiovascular event while receiving sunitinib at FDA-approved or lower doses. Patients with preexisting coronary artery disease were more likely to develop cardiac problems. Nineteen percent of the 36 patients receiving the FDA-approved dose had decreases in left ventricular ejection fraction, a measure of the hearts pumping ability.

In addition, 47 percent (35 of 75) developed hypertension. Hypertension is a common side effect with certain cancer drugs, but the degree of hypertension both the percentage of affected patients and the magnitude of increase in systolic blood-pressure was notable, says Chen, who is also affiliated with Brigham and Womens Hospital, Dana-Farber Cancer Institute and Harvard Medical School.

Two patient biopsies revealed abnormalities in the heart cells mitochondria (the structures responsible for energy production). Further studies, led by Maria Rupnick, MD, of the Childrens Hospital Boston Vascular Biology Program, and Thomas Force, MD, from the Center for Translational Medicine and Division of Cardiology at Jefferson, examined heart-muscle cells from mice who had received the equivalent of a human dosage of sunitinib alone, and found direct evidence of cardiotoxicity.

Early identification of cardiac side effects is an important part of keeping patients on life-saving cancer therapy over the long-term, says Chen. In this study, the cardiac dysfunction and hypertension were usually medically manageable. Most importantly, patients were most often able to resume sunitinib therapy following temporary withholding of drug, addition of cardiac medications and/or dose adjustment.

This sunitinib study highlights potential concerns with agents that are multi-targeted, meaning they inhibit multiple factors involved in cancer progression, adds Force, who led the study of imatinib patients published in Nature Medicine last year. Some of these factors may also play important roles in maintenance of proper heart function, and their inhibition by cancer drugs could have adverse effects on the heart.

The most important element of this new work is the close, creative collaboration between our medical oncology and cardiology teams, says George Demetri, MD, a co-author on the paper and director of the Ludwig Center at Dana-Farber Cancer Institute and Harvard Medical School. As our molecular targeting involves more pathways, we can inform one anothers fields and identify side effects early by working together across traditional disciplinary boundaries.

We are hopeful, Chen concludes, that this type of multidisciplinary approach, from the patients bedside to the basic cell biology laboratory, will lead to further pharmaceutical advances that will make these smart cancer drugs even smarter.

Childrens has a long history of researching the cardiovascular effects of cancer drugs. In children, such side effects are especially important to manage so they can survive the cancer in good health well into adulthood. In 1991, for example, Childrens cardiologists published the seminal finding that doxorubicin therapy for childhood leukemia can lead to clinically important heart disease.


'/>"/>

Contact: Anna Gonski
anna.gonski@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

Related medicine news :

1. Another Reason Not to Smoke While Pregnant: Birth Defects
2. One Species Genome Found Within Another
3. Eat Seafood, See Weight Loss: Recent Study Finds Another Reason to Eat Seafood for a Fit Lifestyle
4. Message for Activists at Latino National Congreso Convention: Amnesty Will Exacerbate National Problems and Turn the U.S. into Another Mexico
5. Latest Edition of Ripon Forum Highlights Schwarzeneggers Leadership on Another Challenge Facing his State - Health Care
6. Beckman Coulter Signs Agreements With Amerinet, Inc.; Ten-Year Partnership Extended for Another Three Years
7. Portico(TM) Systems Charts Another Period of Rapid Growth
8. Another Medtronic Sprint Fidelis Lead Lawsuit is Filed in Federal District Court
9. FDA Sunscreen Labeling Decision Delayed Another Month, Leading U.S. Physician to Say, Enough Is Enough
10. New Smart Technology Makes Patient Data Collection Easier, More Efficient
11. New Survey Shows Americans are Still Concerned About Food Safety, Yet Still Not Smart About What They Like to Eat
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/26/2016)... (PRWEB) , ... June 27, 2016 , ... Quality metrics ... yet in many ways they remain in the eye of the beholder, according to ... a publication of The American Journal of Managed Care. For the full issue, ...
(Date:6/26/2016)... ... June 26, 2016 , ... Many ... been diagnosed with endometriosis. These women need a treatment plan to not only ... approach that can help for preservation of fertility and ultimately achieving a pregnancy. ...
(Date:6/25/2016)... ... 2016 , ... First Choice Emergency Room , the largest network of ... Medical Director of its new Mesquite-Samuell Farm facility. , “We are pleased to ... said Dr. James M. Muzzarelli, Executive Medical Director of First Choice Emergency Room. ...
(Date:6/24/2016)... ... June 24, 2016 , ... A recent article published June ... with. The article goes on to state that individuals are now more comfortable seeking ... common operations such as calf and cheek reduction. The Los Angeles area medical group, ...
(Date:6/24/2016)... ... June 24, 2016 , ... Global law firm Greenberg Traurig, P.A. ... The attorneys chosen by their peers for this recognition are considered among the top ... Shareholders received special honors as members of this year’s Legal Elite Hall of Fame: ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... -- , , , WHEN: , ... , , , LOCATION: , , , Online, with free ... EXPERT PANELISTS:  , , , Frost & Sullivan,s Global Vice President ... Industry Analyst, Divyaa Ravishankar and Unmesh Lal, Program Manager , ... is witnessing an exceptional era. Several new demand spaces, such as ...
(Date:6/23/2016)... , June 23, 2016 Revolutionary ... Oticon , industry leaders in advanced audiology ... of Oticon Opn ™, the world,s first internet ... possibilities for IoT devices.      (Photo: ... introduces a number of ,world firsts,: , ...
(Date:6/23/2016)... 2016 Research and Markets has ... Global Analysis (United States, China, Japan, Brazil, United Kingdom, ... their offering. Surgical ... business planners, provides surgical procedure volume data in a ... an in-depth analysis of growth drivers and inhibitors, including ...
Breaking Medicine Technology: