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Heart Failure Resulting From Trastuzumab (Herceptin) Use Largely Reversible: Presented at HFSA

By Cameron Johnston

TORONTO, ON -- September 15, 2004 -- Cardiotoxic events that occur as a result of treatment with the human monoclonal antibody trastuzumab (Herceptin) are largely reversible, according to a study from the MD Anderson Cancer Center, in Houston, Texas.

The findings were presented here September 13^th at the Heart Failure Society of America 14^th Annual Congress.

Treatment with trastuzumab has usually been restricted to cancer patients who have never been treated with anthracyclines, due to their known cardiotoxic effects, or to patients whose total exposure to anthracyclines has been low, according to the researchers, led by Michael Ewer, MD, Department of Cardiology.

To determine the true risk of cardiotoxicity associated with trastuzumab, researchers reviewed the charts of 35 patients who were receiving trastuzumab and were referred for evaluation of possible left ventricular (LV) dysfunction. All had received prior anthracycline-based chemotherapy and were from a much larger population of patients with breast cancer that were treated with trastuzumab at MD Anderson Cancer Center.

None of the patients had any serious underlying cardiac disease before beginning chemotherapy. Mean ejection fraction decreased to 61% at the end of the chemotherapy course. When the patients were switched to trastuzumab therapy, the mean ejection fraction decreased to 40%; 19 patients were deemed to have developed congestive heart failure. Diagnosis was made by cardiac ultrasound in all patients, and nine underwent right ventricular biopsy.

Of the patients who developed congestive heart failure, standard treatments using angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and beta-blockers, and/or a combination of treatments.

Of the 35 patients enrolled, 34 had at least some recovery of LV function, and after 3 months, mean LV ejection fraction had increased from 40% to 55%.

When 25 of those patients were re-challenged with trastuzumab, three cases of LV dysfunction occurred. The remainder tolerated trastuzumab use with no LV abnormalities.

Dr. Ewer noted that these patients were selected because they had received previous anthracycline therapy and were suspected of having developed LV dysfunction. This does not imply that the percentage of patients who would develop LV dysfunction after using trastuzumab would be as high as what was seen in this study, he added.

In this study, re-treatment with trastuzumab was carried out successfully and safely. The potential benefits of trastuzumab should be weighed against the risk of recurring cardiac events, he said, and in any case, close monitoring for LV dysfunction should be a routine part of clinical practice for any and all patients undergoing these therapies.


[Presentation title: "Reversibility of Trastuzumab-Induced Congestive Heart Failure in Patients Previously Treated With Anthracyclines." Abstract 369]

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