SAN ANTONIOA condensed, 14-day schedule of doxorubicin (Adria-mycin),
cyclophosphamide, and pacli-taxel (Taxol) proved superior to conventional
scheduling of the three drugs in a Cancer and Leukemia Group B (CALGB) trial
reported at the 25th Annual San Antonio Breast Cancer Symposium (abstract
15). According to study investigator Marc L. Citron, MD, the dose-dense
scheduling resulted in significant improvements in both disease-free and
overall survivaland, with filgrastim (Neupogen) support, did not increase
Beginning in 1997, the phase III trial (CALBG 9741) randomized 2,005 women
with node-positive stage II/IIIa breast cancer to one of four regimens of
Adria-mycin (A), 60 mg/m2; cyclophosphamide (C), 600 mg/m2; and
Taxol (T) 175 mg/m2. The regimens were designed to compare
concurrent therapy (AC, followed by T, or AC-T) to sequential therapy (A-T-C)
in both a conventional 21-day schedule and a dose-dense 14-day schedule (see
Table). Cumulative and individual treatment doses were identical
in each arm.
All patients on the two dose-dense regimens also received filgrastim (5
µg/kg, starting on day 3 for a total of seven doses). Upon completion of
chemotherapy, all premenopausal, estrogen-receptor (ER)-positive patients and
all postmenopausal patients were advised, but not required, to begin
tamoxifen (Nolvadex) (20 mg/d) within 12 weeks.
Dr. Citron, clinical professor of medicine, Albert Einstein College of
Medicine, Bronx, New York, noted that patient eligibility requirements were
kept as broad as possible in order to include the types of patients seen in
everyday practice. The study population included T0-T3, N1/N2 patients.
Participants had undergone primary surgery with lump-ectomy and axillary
lymph node dissection or modified radical mastectomy, with clear margins.
Chest x-ray was the only specific staging criterion.
The researchers stipulated a baseline granulocyte count of 1,000 µL for
entry into the trial for the first and every dose of chemotherapy in order to
keep dose reductions and delays to a minimum.
The median patient age was 50, approximately 50% were premenopausal, and
the median number of involved lymph nodes was 3. Approximately one third of
the patients had ER-negative tumors, and about one third had undergone
lumpectomy. Equal numbers of patients in all four arms received tamoxifen. Of
the 2,005 patients enrolled, 1,973 received therapy and were evaluable.
At this first protocol-specified analysis at a median follow-up of 3
years, 315 patients had experienced recurrences, compared with the
approximately 515 recurrences that had been expected.