San Francisco, CA - Patients taking sunitinib (Sutent, Pfizer) will require close cardiac monitoring, a new study suggests [1]. The drug, which is used to treat renal-cell carcinoma and gastrointestinal stromal tumors, has been linked to more heart failure than previously reported. The findings are scheduled to be presented on February 16 here at the 2008 Genitourinary Cancers Symposium.

Speaking to reporters in advance of the meeting, lead author Dr Melinda Telli (Stanford University School of Medicine, Palo Alto, CA) reported that 15% of patients taking sunitinib developed heart failure—more than the previously reported 8%.

The researchers also emphasize that, contrary to previous findings, the effects were irreversible even after stopping therapy.

Sunitinib is an oral small-molecule multitargeted receptor tyrosine kinase inhibitor. It works by inhibiting the growth of blood vessels that tumors need to grow and spread. The drug might also slow the growth and division of cancer cells. Sunitinib is currently being tested for the treatment of a variety of other cancers, both in early and advanced stages.

During an interview, press-conference moderator Dr Howard Sandler (University of Michigan Health System, Ann Arbor) pointed out that the study of just 48 patients was small and questions remain about how reliable the observation is.

"But the findings certainly support the routine cardiac monitoring of patients taking sunitinib," Sandler said. "The researchers were also looking at an unselected patient population from Stanford, and this may have important implications for the general population," he added.

The current study is the first to evaluate adverse cardiovascular effects in patients who were taking sunitinib outside of the context of a clinical trial. Patients with preexisting cardiac conditions, for example, would not have been excluded from this study.

Telli said that although larger studies will need to be conducted, she wonders whether the true incidence of heart failure is even greater than what her group saw.

Sunitinib has also been linked to hypertension. Animal studies have shown that the drug can be toxic to cardiac cells and that this effect might be exacerbated by high blood pressure.

In the current analysis, researchers studied the occurrence of symptomatic heart failure in 48 patients on sunitinib from the Stanford University Comprehensive Cancer Center.

A total of seven patients experienced symptomatic left ventricular dysfunction during treatment. These effects were observed as early as 22 days and as late as 435 days after the start of therapy. Symptoms persisted in three patients despite the discontinuation of sunitinib and the initiation of heart-failure treatment.

The mean age of those experiencing cardiotoxicity was 65 years. Investigators found that patients with a history of heart failure, a history of coronary artery disease, or a low body-mass index were more likely to experience heart failure.

"Cardiac adverse effects need to be carefully examined in future trials of sunitinib to determine the factors that place patients at risk for this complication," Telli told reporters. "That information will allow us to administer this medication more safely to patients for whom the benefits of treatment clearly outweigh the risks."

Such trials are urgently needed, she noted, because plans are under way to expand the oncologic indications for this drug.