Sunitinib – a tyrosine-kinase inhibitor used to extend survival in patients with renal-cell carcinoma and gastrointestinal stromal tumours – has cardiotoxic effects. As such, patients given sunitinib, especially those with cardiac risk factors – need to be closely monitored. These are the conclusions of authors of an Article published in this week’s edition of The Lancet.
Dr Ming Hui Chen, Cardiology Department, Children’s Hospital Boston, MA, USA, and colleagues, studied 75 adult patients with metastatic, gastrointestinal stromal tumours, which had not responded to imatinib (the standard treatment); these patients had subsequently been enrolled in a phase I/II trial investigating the efficacy of sunitinib. Cardiac death, heart attack and congestive heart failure were the endpoints of the study. The researchers also investigated the effect of sunitinib on left ventricular ejection fraction (LVEF) and blood pressure.
They found that eight of the 75 patients given repeating cycles of sunitinib had a cardiovascular event – two had heart attacks, while the other six had heart failure. Of 36 patients given the approved sunitinib dose, 10 (28%) experienced reductions in LVEF of 10% or more, while seven (19%) experienced LVEF reductions of 15% or more. Sunitinib also induced increases in mean systolic and diastolic blood pressure, with 35 of 75 patients (47%) developing hypertension. Heart failure and left ventricular dysfunction generally improved when sunitinib was withdrawn and medical management was implemented. Further, sunitinib caused mitochondrial injury and death of cardiomyocyte cells in rodents.
The authors conclude: “Our findings reveal evidence of sunitinib-associated heart failure, left ventricular systolic dysfunction, and hypertension in patients with imatinib-resistant, metastatic gastrointestinal stromal tumours. Cardiovascular adverse events were medically manageable in most patients. Close monitoring could be a prudent approach until large studies can clearly define the nature and rate of sunitinib-associated cardiovascular effects, especially in patients with cardiac risk factors, or history of coronary artery disease, or both.”
In an accompanying Comment, Dr Heikki Joensuu, Helsinki University Central Hospital, Finland, says: “Patients treated with sunitinib need careful monitoring not only for hand-foot syndrome and other well-established adverse effects but also for thyroid and cardiac function. Although data are limited and more research is needed, sunitinib might be at least as cardiotoxic as trastuzumab.”
The paper associated with this release is at http://multimedia.thelancet.com/pdf/press/Cardiotoxicity.pdf
For Dr Ming Hui Chen, Cardiology Department, Children’s Hospital Boston, MA, USA please contact Anna Gonski T) +1 617-919-3110 E) minghui.chen@cardio.chboston.org
Dr Heikki Joensuu, Helsinki University Central Hospital, Finland E) heikki.joensuu@hus.fi
Journal
The Lancet