SAN ANTONIOIn the treatment of breast cancer, cardiomyopathy has represented a possible barrier to the use of trastuzumab(Drug information on trastuzumab) (Herceptin) in the adjuvant setting. But a study by the Eastern Cooperative Oncology Group (ECOG) now suggests the risk is small when trastuzumab is combined with paclitaxel(Drug information on paclitaxel) (Taxol), and, for the most part, cardiac changes are reversible.
George W. Sledge, MD, professor of medicine, Indiana University School of Medicine, presented the results at the 24th Annual San Antonio Breast Cancer Symposium (abstract 4). ECOG 2198 examined the cardiac effects of paclitaxel plus trastuzumab (TH) given prior to doxorubicin(Drug information on doxorubicin) plus cyclophosphamide(Drug information on cyclophosphamide) (AC) in 234 HER-2-positive (2+ or 3+) stage II breast cancer patients.
Patients were randomized to paclitaxel 175 mg/m² every 3 weeks for 4 weeks plus trastuzumab for 10 weeks followed by AC (60/600 mg/m²) every 3 weeks for 4 weeks, or to the same treatment with trastuzumab given for 52 weeks.
"We now know that the underlying hypothesis about Herceptin clearance was probably incorrect," Dr. Sledge pointed out. "Patients who got Herceptin for 10 weeks probably still had a significant amount of Herceptin on board when they got AC."
The endpoints were the rate of clinical congestive heart failure (CHF) and greater than 10% absolute decline in left ventricular ejection fraction (LVEF).
Four Cases of CHF
At 15 months median follow-up, there were four cases of clinical CHF during treatment (1.7%), including one patient during TH and three after receiving the AC regimen. There were no cardiac fatalities. "It’s instructive to look at these four events," Dr. Sledge said, describing the CHF patients, all of whom had predisposing factors for organic heart disease: