The Pharmaceutical Journal
Vol 277 No 7483 p704
22/29 December 2007

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Sunitinib-linked cardiotoxicity highlighted

Evidence of sunitinib-associated cardiotoxicity has emerged in a study of 75 patients with imatinib-resistant metastatic gastrointestinal stromal tumours (Lancet 2007;370:2011).

Researchers in the US reviewed all cardiovascular events in these patients who had been enrolled in a phase I/II trial and treated with sunitinib (Sutent). The endpoints were cardiac death, myocardial infarction and congestive heart failure. The effects of sunitinib on left ventricular ejection fraction and blood pressure were also measured. Median follow up was 33.5 weeks.

The researchers found that eight patients (11 per cent) suffered a cardiovascular event — two had a myocardial infarction and four had congestive heart failure while receiving multiple cycles of sunitinib. Those with a history of coronary artery disease were more likely to develop cardiac problems.

A reduction in left ventricular ejection fraction of 10 per cent or more was observed in 10 of 36 patients (28 per cent) who received the approved dose of sunitinib, with seven (19 per cent) experiencing reductions of 15 per cent or more. In addition, sunitinib increased systolic and diastolic blood pressure, with 35 patients (47 per cent) developing hypertension.

The researchers found that left ventricular dysfunction and symptoms improved in five of six congestive heart failure patients after dose interruption, modification or initiation of heart failure therapy. “Sunitinib was restarted in all five patients without recurrence of heart failure. However, four patients had episodic LVEF reductions after restarting sunitinib,” they add.

The researchers also conducted experiments in rodents, which showed that sunitinib caused mitochondrial injury and death of cardiomyocyte cells.

“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,” the researchers conclude.