If this is not your name, click here.
| | If this is not your name, click here. | | |
| | Contact Us | Order Now | Journals | Bookstore | Register a colleague | | |
| |  SABCS: Risk of Congestive Heart Failure Low with Taxol (Paclitaxel)-Herceptin (Trastuzumab) Adjuvant Therapy By Ed Susman SAN ANTONIO, TX -- December 12, 2001 -- Although there appears to be a risk of developing congestive heart failure among women taking the human epidermal growth factor receptor 2 (HER2)-neu antagonist Herceptin (trastuzumab) along with chemotherapy, this risk appears to be small and, for the most part, those heart changes are reversible. In a study reported at the 24th Annual San Antonio Breast Cancer Symposium, George Sledge, MD, a professor of medicine at University of Indiana, in Indianapolis, Indiana, said that it might be possible to limit the damage to a patient’s heart by administering a combination of trastuzumab and Taxol (paclitaxel) prior to anthracyclines. Dr. Sledge said only four of more than 230 patients in the study were taken off treatment because of the appearance of congestive heart failure or a decrease in left ventricular ejection fraction (LVEF) from baseline by 20 percent or more. "Looking at our primary end point," he said, referring to the cardiomyopathy, "four patients developed clinical congestive heart failure at some time during the course of their therapy, for an overall incidence of 1.7 percent. One developed heart failure while on Taxol-Herceptin, the other three during Adriamycin (doxorubicin)-Cytoxan (cyclophosphamide). There have been no cardiac fatalities. Those four patients who developed heart failure entered the study with heart abnormalities. All the patients who experienced these depressed heart functions showed substantial rebound with change in medication, he reported. "Doxorubicin-based chemotherapy is a standard adjuvant therapy for HER2-neu breast cancer patients," Dr. Sledge said. "Trastuzumab is associated with an increased risk of cardiomyopathy when given after anthracycline-based adjuvant chemotherapy," he explained. "The objectives of this trial were to evaluate the safety of paclitaxel plus trastuzumab as a combination when administered prior to doxorubicin and cyclophosphamide for patients receiving adjuvant therapy for lymph node-positive breast cancer. In addition, we wished to evaluate the safety of chronic trastuzumab therapy for patients receiving adjuvant therapy for lymph node-positive disease." Patients in the trial were HER2 positive and had lymph node-positive breast cancer. All patients had to have a resting LVEF greater than 50 percent. Following testing for HER2, patients were randomised to one of two arms. In the first arm, patients received Taxol 175 mg/m² every three weeks for a total of four cycles and Herceptin starting dose 4 mg/kg and then, 2 mg/kg weekly for a total of 10 weeks. Patients stopped Herceptin three weeks prior to the first planned dose of Adriamycin and Cytoxan. Patients received Adriamycin and Cytoxan at standard doses of 60 mg/m² and 600 mg/m² every three weeks for four cycles. In the second arm of the trial, patients received the same therapy as in the first arm but, in addition, received Herceptin for a subsequent 52 weeks of therapy. Cardiac monitoring was performed. Patients' LVEF was measured at baseline, immediately prior to Adriamycin and Cytoxan, immediately after Adriamycin and Cytoxan, at six months, and then at one year. Patients were taken off trastuzumab if their LVEF decreased by more than 20 percent or if they developed clinical congestive heart failure. "We had an initial accrual of 110 patients and this was subsequently increased to another 220 patients to allow [for] higher confidence intervals in our primary and secondary end points," Dr. Sledge said. In 214 patients evaluable after Taxol-Herceptin, mean baseline LVEF was 63 percent, which decreased to 61 percent following Taxol-Herceptin, Dr. Sledge said. Twenty patients (9 percent) had an LVEF decrease greater than 10 percent; six patients (2.8 percent) had LVEF decreases below the lower limits of normal. The majority of these patients had their LVEF recover despite going on to receive Adriamycin and Cytoxan. Mean LVEF decreased from 63 percent at baseline to 59 percent after Adriamycin-Cytoxan. Twenty-four patients (13 percent) had a decrease in their LVEF of greater than 10 percent, and 11 patients (6 percent) had a decrease to a level lower than the institutional limits of normal. "Taxol-Herceptin, followed by Adriamycin-Cytoxan, is associated with a low but real incidence of congestive heart failure, [somewhat] less than 2 percent in this trial," Dr. Sledge said. "Overall, I think we should find this data relatively comforting."
|
