PITTSBURGH, July 18 -- Although trastuzumab (Herceptin) has been lauded as being beneficial in the treatment of breast cancer, its use is associated with a high incidence of cardiac toxicity and raises important questions about mechanisms of action, appropriate patient monitoring and risk/benefit ratio, according to a report by a cardiologist at the University of Pittsburgh Medical Center published in the current issue of Circulation.
The report further states that the extension of trastuzumab use to patients with less invasive forms of breast cancer seems imprudent in view of untoward cardiac effects and should be reconsidered until additional information is available.
"As cited in FDA product labeling, a substantial number of women treated with trastuzumab developed congestive heart failure; seven percent when receiving the drug alone in an open label study, and 28 percent when treated with a combination of trastuzumab, anthracycline and cyclophosphamide," reports Arthur Feldman, M.D., Ph.D., director of the Cardiovascular Institute at the University of Pittsburgh Medical Center and author of the report. "Despite oncologists' enthusiasm for this drug as a cancer treatment, the potential significance of the high incidence of trastuzumab-induced cardiotoxicity deserves attention."
According to the report, long-term survival of women with congestive heart failure (33 percent at six years) approximates that of women with breast cancer and distant metastases (22 percent at five years), but it is worse than that of women with breast cancer and regional metastases (77 percent at five years).
No prospective studies have assessed trastuzumab-induced cardiotoxicity. The rapid increase in trastuzumab use and the planned expansion of its use to breast cancer patients without metastasis and to patients with other forms of cancer mandates that such information be obtained in a timely fashion, he explains.
While most women who developed heart failure after trastuzumab therapy had symptomatic improvement with appropriate cardiac therapy, heart failure, like many cancers, is a progressive disease and mortality remains high despite improvement in symptoms, writes Dr. Feldman.
According to the report, the warning label in the package insert suggests that the drug should be discontinued in patients with a "clinically significant" decrease in ventricular function. However, "clinically significant" is undefined and there is no information to identify which clinical tests would be appropriate for assessing cardiac function in these patients.
"A conundrum that overshadows attempts to evaluate trastuzumab cardiotoxicity is the complete lack of information regarding its short- and long-term effects on cardiac structure and function," Dr. Feldman writes.
"It is imperative that we perform long-term cardiac follow-up of women receiving the drug and that we learn more about its cardiotoxicity to ensure that patients do not trade one lethal disease for another," he said. "It is also critical to perform studies to understand whether patients with asymptomatic coronary disease or left ventricular hypertrophy are at increased risk."
CONTACT:Frank Raczkiewicz
Jennifer Bielata
412-647-3555
FAX: 412-624-3184
raczkiewiczfa@msx.upmc.edu
bielatajl@msx.upmc.edu