A retrospective analysis found a risk for heart failure, heart attacks and hypertension, a bit of a surprise given that the cancer drug was originally thought to be free of side effects. The study, which was conducted by researchers at Children’s Hospital Boston, the Dana-Farber Cancer Institute and Thomas Jefferson University, appears in The Lancet.

This is the second time a so-called smart cancer drug known as a tyrosine kinase inhibitor has been associated with heart problems. Last year, the problem showed up in patients with chronic myelogenous leukemia who had taken Novartis’ Gleevec. These drugs target specific signaling molecules inside cancer cells that aid the spread of cancer.

“This study highlights potential concerns with agents that are ‘multi-targeted,’ meaning they inhibit multiple factors involved in cancer progression,” says Thomas Force, one of the co-authors, who also led the study of Gleevec 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.”

This is the study.

The analysis, which focused on cardiovascular events, found the risks in 75 adult patients with Gleevec-resistant, gastrointestinal stromal tumor (GIST) receiving multiple cycles of Sutent in a Phase I/II trial.

Of the 75, six, or 8 percent developed symptoms consistent with moderate-to-severe congestive heart failure, and two had heart attacks. In all, eight patients, or 11 percent had some kind of cardiovascular event while receiving Sutent at FDA-approved or lower doses. Patients with pre-existing coronary artery disease were more likely to develop cardiac problems. Nineteen percent of the 36 patients receiving the FDA-approved dose had clinically significant decreases in left ventricular ejection fraction, a measure of the heart’s pumping ability.

In addition, 47 percent (or 35 of 75 patients) 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 Ming Hui Chen, a co-author and cardiologist at Children’s who specializes in the cardiac health of cancer patients.

“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 patients were able to resume sunitinib therapy following temporary withholding of drug, addition of cardiac medications and/or dose adjustment.”

In a statement, Pfizer says “the risk-benefit profile of Sutent has been well-established through large, randomized clinical trials evaluating the safety and efficacy in both advanced renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST).” The drugmaker goes on to say that the CV events found in the new analysis were “medically manageable in most patients and underscore the importance of having a collaborative team of healthcare professionals working together to appropriately manage patients, who have limited additional options. Close monitoring is recommended, especially in patients with cardiac risk factors and a history of coronary artery disease.

“Lower incidences of cardiovascular effects have been observed in subsequent randomized Phase III prospective Sutent studies in both RCC and GIST including the incidences of congestive heart failure, ejection fraction decline (EF) and hypertension than were shown in this small retrospective analysis. The Phase III data are included in the current FDA approved labeling for Sutent which suggests cardiac monitoring in patients with cardiac risk factors. To date, more than 33,000 patients have been treated with Sutent in the clinical setting and trials.”