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:5/24/2017)... ... 2017 , ... Medic CE , a Career Step company, is sponsoring ... hosted by the Journal of Emergency Medical Services (JEMS). The free webinar, to be ... by Captain Rommie Duckworth, LP, a career fire captain as well as founder and ...
(Date:5/24/2017)... ... , ... Rob Lowe is a sought after actor, and also serves as ... public important topics from all aspects of life, and a new segment is being ... and ankles. , Podiatry is essential to people’s overall well-being, and if viewers have ...
(Date:5/24/2017)... Shoreview, MN (PRWEB) , ... May 24, 2017 ... ... manufacturer of polyvinylidene fluoride (PVDF) based sleep diagnostics sensors, announced today it had ... network now consists of a mix of domestic and rest of world (ROW) ...
(Date:5/23/2017)... NEW YORK, NY (PRWEB) , ... May 23, ... ... decision makers in the pharmaceutical and medical device sectors, today announced the winners ... • Transformers • Entrepreneurs) represent the most influential people in the healthcare industry ...
(Date:5/23/2017)... , ... May 23, 2017 , ... ... body for exercise professionals, is pleased to announce the organization’s Certified Strength Coach ... The NCSF Certified Strength Coach (CSC) program validates the competency of qualified candidates ...
Breaking Medicine News(10 mins):
(Date:5/8/2017)... 8, 2017 MACRA replaces the outdated ... for service reimbursement. Black Book Research crowdsource-surveyed 8,845 physician ... 1.       The Market for MIPS Compliance Technology is Booming ... practices with 3 or more clinicians seek to buy ... "Given the magnitude of the changes, the hunt is ...
(Date:5/4/2017)... 2017  Fortuna Fix Inc. (" Fortuna "), a ... to eliminate the need for embryonic and fetal stem cells ... diseases. Fortuna announced today the launch ... Fehlings , MD, PhD; Father Kevin FitzGerald , S.J., ... Professor James Giordano , PhD. "We are ...
(Date:5/4/2017)... WAYNE, Pa. , May 4, 2017 /PRNewswire/ ... made from thermoplastics and other highly-engineered materials, is ... Microextrusion tubing has been developed in recent ... neurovascular interventional therapies and surgical applications. More expensive ... used to produce microextrusion tubing due to their ...
Breaking Medicine Technology: