LOS ANGELES--Sequential chemotherapy including an anthracycline produced better overall and relapse-free survival in women with node-positive breast cancer (more than three nodes) than did an alternating schedule of the same drugs, Gianni Bonadonna, MD, of the Istituto Nazionale Tumori, Milan, reported at the ASCO annual meeting.
The sequential adjuvant regimen consisted of four courses of doxorubicin(Drug information on doxorubicin) followed by eight cycles of CMF (cyclophosphamide, methotrexate(Drug information on methotrexate), and fluorouracil(Drug information on fluorouracil)). The alternating schedule called for two courses of CMF interspersed with one cycle of doxorubicin.
These 10-year results confirm and extend the Milan trial's 5-year findings, reported previously, said Dr. Bonadonna, director, Division of Medical Oncology. "Our data on Adriamycin followed by CMF are sufficiently mature and valid to advise replacing in clinical practice the classical CMF with Adriamycin followed by CMF in the adjuvant treatment of women with more than three positive nodes," he said.
About two thirds (67%) of the 403 women in the study (all aged 70 years or less with resectable primary breast tumors and more than three positive axillary lymph nodes) underwent a modified radical mastectomy, and 33% had breast-conserving surgery with full axillary node dissection followed by postoperative irradiation.
Within 4 weeks of surgery, patients were randomized to either the sequential or alternating chemotherapy regimen. Both regimens were repeated every 3 weeks for a total duration of 33 weeks.
The dose of doxorubicin used, 75 mg/m², was considered a full adjuvant dose in patients with breast cancer at the time of the study's inception in the early 1980s, Dr. Bonadonna noted. Doses for the other agents were 600 mg/m² of cyclophosphamide(Drug information on cyclophosphamide), 40 mg/m² of methotrexate, and 600 mg/m² of fluorouracil.
The rate of relapse-free survival at 10 years was significantly higher in patients treated with sequential therapy than in those given alternating therapy (42% vs 28%), as was the 10-year overall survival rate (58% vs 44%), Dr. Bonadonna reported. Median relapse-free survival was about twice as long in the sequential vs the alternating group (86 vs 46 months).