Sunitinib treatment requires close monitoring for cardiotoxicity

December 13, 2007

NEW YORK (Reuters Health) - Treatment with sunitinib, a tyrosine kinase inhibitor used for metastatic renal cell cancer and gastrointestinal stromal tumors (GIST), can cause hypertension and left ventricular dysfunction and patients should therefore be watched closely, especially if they have a history of heart disease, new research shows.

"Patients treated with sunitinib should be carefully monitored for signs of heart failure such as dyspnea, shortness of breath and edema, and hypertension, which should be aggressively controlled," senior author Dr. Ming Hui Chen told Reuters Health. "With careful monitoring and prompt medical attention, patients can continue to remain on sunitinib therapy for tumor control while minimizing the potential side effects on the heart."

The findings, which appear in the December 15th issue of The Lancet, are based on a review of cardiovascular events in 75 patients with metastatic GIST who participated in a phase I/II trial of sunitinib.

A cardiovascular event was defined as cardiac death, MI, or congestive heart failure. In addition, the researchers examined the impact of sunitinib on blood pressure and left ventricular ejection fraction (LVEF).

Eight patients experienced a cardiovascular event, with congestive heart failure occurring in six, Dr. Chen, from Children's Hospital Boston, and colleagues note. Of 36 patients treated with the approved dose of sunitinib, 10 had a LVEF drop of 10% or greater, including 7 with a reduction of 15% or more.

Sunitinib use was also associated with increases in both systolic and diastolic blood pressure and 35 patients developed hypertension (>150/100 mm Hg).

Left ventricular dysfunction and congestive heart failure usually responded to withholding sunitinib and instituting appropriate medical management.

Analysis of sunitinib's effects in mice and in cultured rat cardiomyocytes suggested that the drug's impact on left ventricular function was due, at least in part, to direct cellular toxicity.

"Tyrosine kinase inhibitors...are an important contribution to oncology and medicine, as they have given hope to patients with cancers that currently have no viable treatment," Dr. Chen emphasized. "We need further studies to determine the best methods of cardioprotection in patients treated with these important anti-cancer drugs."