Another Smart Cancer Drug Can Have Toxic Effects On Heart
Smart Cancer Drug
Another FDA-approved targeted cancer drug, sunitinib, may be associated with cardiac toxicity, report researchers at Children's Hospital Boston, Dana-Farber Cancer Institute (Boston), and Thomas Jefferson University (Philadelphia).
Sunitinib is one of several new "smart" cancer drugs called tyrosine kinase inhibitors that targets specific signaling molecules inside cancer cells that aid cancer spread. Another "targeted" cancer therapy, imatinib (GleevecTM, Novartis Pharmaceuticals), was reported last year by cardiologist Thomas Force, M.D., James C. Wilson Professor of Medicine at Jefferson Medical College in the Center for Translational Medicine and the Division of Cardiology, in the journal Nature Medicine to be associated with heart failure in patients with chronic myelogenous leukemia.
Sunitinib was originally thought to be relatively free of cardiac side effects. However, a new retrospective analysis, focused on cardiovascular events, revealed a risk for heart failure, myocardial infarction and hypertension in 75 adult patients with imatinib-resistant, gastrointestinal stromal tumor (GIST) receiving multiple cycles of sunitinib in a phase I/II trial at Dana-Farber.
Of the 75, six (8 percent) developed symptoms consistent with moderate-to-severe congestive heart failure, and two had heart attacks. In all, eight (11 percent) had some kind of cardiovascular event while receiving sunitinib at FDA-approved or lower doses. Patients with preexisting coronary artery disease were more likely to develop cardiac problems. Nineteen percent of the 36 patients receiving the FDA-approved dose had decreases in left ventricular ejection fraction, a measure of the heart's pumping ability.
In addition, 47 percent (35 of 75) 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 Dr. Chen, who is also affiliated with Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School.
Two patient biopsies revealed abnormalities in the heart cells' mitochondria (the structures responsible for energy production). Further studies, led by Dr. Force and Maria Rupnick, M.D., of the Children's Hospital Boston Vascular Biology Program, examined heart-muscle cells from mice who had received the equivalent of a human dosage of sunitinib alone, and found direct evidence of cardiotoxicity.
"Early identification of cardiac side effects is an important part of keeping patients on life-saving cancer therapy over the long-term," says Dr. Chen. "In this study, the cardiac dysfunction and hypertension were usually medically manageable.