SAN ANTONIO—A condensed, 14-day schedule of doxorubicin(Drug information on doxorubicin) (Adria-mycin), cyclophosphamide(Drug information on 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 survival—and, with filgrastim(Drug information on filgrastim) (Neupogen) support, did not increase drug toxicity.
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(Drug information on 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.
