LOS ANGELES--An aggressive 16-week, multidrug chemotherapy regimen afforded a survival advantage over six cycles of CAF (cyclophosphamide, Adriamycin, and fluorouracil(Drug information on fluorouracil)) in 646 women with receptor-negative, node-positive breast cancer, preliminary results of an Intergroup study have shown.
In this early analysis, women treated with the 16-week regimen had a better 3-year overall survival rate than those who received CAF (84% vs 76%), John H. Fetting, MD, associate professor of oncology, The Johns Hopkins University School of Medicine, reported at the American Society of Clinical Oncology (ASCO) meeting.
Disease-free survival at 3 years also favored the 16-week treatment program (71% vs 64%, respectively). Although there was a trend toward fewer recurrences in the group treated with the 16-week regimen, this difference did not reach statistical significance, Dr. Fetting said.
Just over half of the study participants were premenopausal, slightly more than half had between 1 and 3 positive nodes, and the majority (more than 85%) had T1 or T2 tumors.
Patients assigned to the CAF arm received six 28-day cycles of CAF, whereas those randomized to the 16-week regimen received eight 2-week cycles, in which cyclophosphamide(Drug information on cyclophosphamide), doxorubicin(Drug information on doxorubicin), vincristine, methotrexate(Drug information on methotrexate), fluorouracil, and leucovorin were given on odd-numbered weeks and a 2-day continuous infusion of fluorouracil was given on even-numbered weeks.
The 16-week regimen developed at Johns Hopkins is based on three principles: (1) rapid exposure of the tumor to multiple active agents, (2) dose intensity, and (3) optimal administration of antimetabolites.
Dose intensity, in particular, may have been responsible for the superior survival attained with the 16-week regimen, Dr. Fetting said. The dose of doxorubicin in the 16-week regimen was 30% higher than that in the CAF regimen (17 vs 13 mg/m²/wk) and the fluorouracil dose was approximately 2.5 times higher (534 vs 219 mg/m² /wk), he noted. The addition of methotrexate and vincristine to the 16-week regimen may also have contributed to the favorable results.