Targeted cancer drug poses heart risk

Another powerful new targeted cancer drug has been found to damage the heart, prompting researchers to urge that all patients be closely monitored for high blood pressure and heart failure.

Pfizer Inc.'s Sutent, approved a year ago to treat a rare stomach cancer and advanced kidney cancer, is the latest in the growing arsenal of molecular-based therapies to show that even a targeted attack may cause serious collateral damage.

Last year, a small increased risk of heart failure was linked to Gleevec, which treats a type of leukemia. Cardiac toxicity is also a well-known problem with Herceptin, the breakthrough breast-cancer drug that in the late 1990s ushered in the era of targeted cancer medicine.

"It's still fair to say many of these agents are less toxic than traditional cancer drugs. They really have revolutionized the treatment of some cancers," said Thomas Force, a Thomas Jefferson University cardiology researcher who coauthored the new Sutent study as well as the Gleevec paper. "But the same molecules that drive cancer may be involved in normal cell function."

Sutent has been used by more than 33,000 patients, according to Pfizer. In a statement, the company said the labeling for Sutent already suggests heart monitoring for patients with cardiac risk factors.

The findings "underscore the importance" of having a variety of specialists involved in cancer care, the company said.

The new study has implications for the growing class of "kinase inhibitors" that target not just one or two but many molecular pathways exploited by cancer. Sutent, for example, inhibits proteins that enable cancer cells to divide like mad, as well as proteins that tumors need to grow their own blood vessels.

The U.S. Food and Drug Administration has approved six multi-kinase inhibitors since 2001, and hundreds more are in development.

The problem is that with more targets comes a greater chance of inadvertent hits. The effects can range from relatively minor nausea, diarrhea and fatigue to serious organ damage.

"Studies that evaluate cardiac effects of other multiple kinase inhibitors are needed," Heikki Joensuu, an oncologist at Helsinki University, concluded in an editorial accompanying the Sutent study.

Jefferson researchers collaborated with colleagues at Children's Hospital of Boston and Dana-Farber Cancer Institute on the study, which appears in the current issue of the Lancet.

They collected heart function and blood pressure data on patients with gastrointestinal stromal tumors throughout a two-year trial of Sutent, also called sunitinib. All 75 patients started out with normal heart function, although four had a history of coronary artery disease.

Eleven percent developed heart problems - six patients were diagnosed with heart failure and two with heart attacks. In addition, almost half developed high blood pressure.

"Hypertension is a common side effect with certain cancer drugs, but the percentage of affected patients and the magnitude of increase in blood pressure were notable," said senior author Ming Hui Chen, a cardiologist at Children's Hospital of Boston and Brigham and Women's Hospital.

The researchers stressed that the results should not scare people away from Sutent - the benefits far outweigh the risks. The drug has been shown to dramatically lengthen survival in patients who basically had no other options.

But oncologists should be alert for signs of cardiac side effects such as high blood pressure, shortness of breath, or swollen ankles. Prompt diagnosis and treatment with heart medication enabled most patients in the study to go back on Sutent after a hiatus.

"It appears that much of this [toxicity] is reversible if treated promptly," said Force, the Jefferson researcher.

In contrast, some traditional chemotherapies and radiation can cause progressive, irreparable heart damage, and it may not show up for years after cancer treatment.