Pfizer's oncology agent Sutent has cardiotoxic effects and patients with heart risk factors need to be closely monitored, according to a new study published in this week’s edition of The Lancet.

Dr Ming Hui Chen and colleagues at the Children’s Hospital Boston, USA, studied 75 adults with metastatic, gastrointestinal stromal tumours, which had not responded to Novartis' Gleevec/Glivec (imatinib), the standard treatment. These patients had subsequently been enrolled in a Phase I/II trial investigating the efficacy of Sutent (sunitinib), which is also approved to treat advanced kidney cancer.

The researchers 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 experienced reductions in left ventricular ejection fraction (LVEF) of 10% or more, while seven experienced LVEF reductions of 15% or more. Sunitinib also induced increases in mean systolic and diastolic blood pressure, with 35 of the 75 patients developing hypertension.

Heart failure and left ventricular dysfunction generally improved when sunitinib was withdrawn and medical management was implemented, the researchers said. They added that Sutent caused mitochondrial injury and death of cardiomyocyte cells in rodents.

The authors concluded that "our findings reveal evidence of sunitinib-associated heart failure, left ventricular systolic dysfunction, and hypertension in patients with imatinib-resistant, metastatic gastrointestinal stromal tumours". They went on to say that cardiovascular adverse events were medically manageable in most patients. but "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, Heikki Joensuu of the Helsinki University Central Hospital, Finland, says that patients treated with Sutent 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, Dr Joensuu said that sunitinib might be at least as cardiotoxic as Roche/ Genetech's Herceptin (trastuzumab).

In response, Pfizer said that larger studies of the drug showed lower incidences of heart effects, including heart failure, high blood pressure and reduced pumping function and "these data are included in the current US Food and Drug Administration-approved labeling for Sutent, which suggests cardiac monitoring in patients with cardiac risk factors".