Cardiac risk low with dose-dense chemo plus trastuzumab for breast cancer

March 11, 2008

NEW YORK (Reuters Health) - In patients with early stage breast cancer, accelerating the dosing schedule of conventional chemotherapy and adding adjuvant trastuzumab appears to be safe, with low rates of cardiac toxicity, according to researchers at New York's Memorial Sloan-Kettering Cancer Center.

Previous studies have shown that when doxorubicin and cyclophosphamide (AC) are administered every 2 weeks instead of every 3 weeks, and followed by paclitaxel, the likelihood of survival is improved and the risk of cancer recurrence is lowered -- without increased cardiac toxicity.

Treatment with trastuzumab further improves outcome in patients with tumors that overexpress the HER-2/neu oncogene, Dr. Chau Dang and colleagues note in the March 10 Journal of Clinical Oncology. This prompted them to explore the safety of AC followed by paclitaxel combined with trastuzumab.

The treatment schedule in their phase II trial consisted of four cycles of AC every 2 weeks followed by four cycles of paclitaxel every 2 weeks. Trastuzumab was administered for 1 year, starting with the first paclitaxel cycle (4 mg/kg bolus followed by 2 mg/kg weekly), then continued at 6 mg/kg every 3 weeks.

The study included 70 patients with HER-2/neu-overexpressing breast cancer and baseline LVEF of 55% or higher.

Trastuzumab was discontinued permanently before 52 weeks in two patients with asymptomatic LVEF declines, one patient with symptomatic congestive heart failure, and three patients for personal reasons.

The 91% completion rate for a full year of trastuzumab compares favorably to previous clinical trials in which trastuzumab was discontinued in nearly one third of patients, Dr. Dang's team points out.

"Dose-dense AC followed by paclitaxel/trastuzumab followed by trastuzumab is feasible," they maintain, "and is not likely to increase the incidence of cardiac events compared to established regimens."