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
The sequential adjuvant regimen consisted of four courses of doxorubicin
followed by eight cycles of CMF (cyclophosphamide, methotrexate,
and 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,
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).