SAN ANTONIOThe addition of docetaxel (Taxotere) to the
combination of doxorubicin (Adriamycin) and cyclophosphamide (AC) is
an effective and safe first-line therapy for women with metastatic
breast cancer, Jean-Marc A.Nabholtz, MD, said at a poster session of
the 21st Annual San Antonio Breast Cancer Symposium.
Notably, the combination did not cause an increase in cardiotoxicity,
said Dr. Nabholtz, chairman of the Northern Alberta Breast Cancer
Program and senior medical oncologist at the Cross Cancer Institute,
Edmonton, Alberta, Canada.
The phase II multicenter study included 55 patients with previously
untreated metastatic breast cancer who received doxorubicin, 50
mg/m² as an intravenous bolus, followed by cyclophosphamide, 500
mg/m² as an intravenous bolus, and docetaxel, 75 mg/m², 1
hour later as a 1-hour infusion. The regimen, referred to as TAC, was
repeated every 3 weeks.
Patients who had received prior chemotherapy for metastatic disease
or an anthracycline-containing regimen as adjuvant and/or neoadjuvant
chemotherapy were not eligible. The patients median age was 53
years; 32% had received prior adjuvant chemotherapy, and 54% had
three or more organs involved.
Of 47 patients evaluable for response, the overall response rate was
77%. The response rate was 79% in the 42 patients with measurable
disease. Responses were observed at all sites, especially in patients
with liver (80%), lung (90%), visceral (57%), or bone (82%) metastases.
The median duration of response was 59 weeks, and the time to disease
progression was 47 weeks. With a median follow-up of 23 months, the
median survival has not yet been reached, Dr. Nabholtz said. Overall,
57% of patients were alive at 2-year follow-up.
The combination was relatively well tolerated. The most common
adverse effects included brief episodes of neutropenia and fever
without a documented infection, which were effectively treated with
antibiotics and did not necessitate a decrease in dose intensity.
Despite a high median cumulative dose of docetaxel (561 mg/m²),
severe fluid retention was noted in only one patient, and no patients
discontinued therapy because of fluid retention. Congestive heart
failure occurred in two patients at a cumulative doxorubicin dose of
greater than 400 mg/m² and was fatal for one.
Our results in this trial strongly suggest that combining
Taxotere with AC enhances overall antitumor activity without
increasing side effects, Dr. Nabholtz concluded.