SAN ANTONIOSequential therapy with three cycles of fluorouracil(Drug information on fluorouracil), epirubicin (Ellence) 100 mg/m2, and cyclophosphamide(Drug information on cyclophosphamide) (FEC-100) followed by three cycles of docetaxel(Drug information on docetaxel) (Taxotere) improved outcomes over six cycles of FEC alone, in node-positive breast cancer patients over the age of 50. Professor Henri Roche, Institut Claudius Regaud, Tou-louse, France, reported the results of the multicenter study from France and Belgium at the 27th Annual San Antonio Breast Cancer Symposium (abstract 27). While the study also included younger women, the significant improvements in disease-free and overall survival were limited to women aged 50 and older.
The study randomized 1,999 patients with node-positive breast cancer to receive either six cycles of FEC-100 every 21 days or three cycles of FEC every 21 days followed by three cycles of docetaxel every 21 days. Half the patients had breast-conserving surgery, and 62% had one to three positive nodes. The FEC-only regimen consisted of fluorouracil 500 mg/m2, epirubicin(Drug information on epirubicin) 100 mg/m2, and cyclophosphamide 500 mg/m2 on day 1, repeated every 3 weeks for six cycles. The FEC/docetaxel regimen used FEC100 for three cycles, then docetaxel 100 mg/m2 on day 1 for an additional three cycles.
Dr. Roche noted that FEC-100 is a standard adjuvant regimen in France, and that docetaxel has been shown to produce very high response rates as first-line therapy. FEC in combination with docetaxel, however, has not been adequately evaluated. Therefore, he said, this study was designed and is "the largest phase III trial of epirubicin-based therapy, the largest with docetaxel, and the first to use these agents in a sequential manner."
In an intent-to-treat analysis performed at a median follow-up of 5 years, treatment with the FEC/docetaxel regimen improved disease-free survival and extended overall survival, Dr. Roche said.
Relapses (see Table) occurred in 482 patients during the study, including 218 on FEC/docetaxel (21.7%) and 264 (26.5%) on FEC-only. The absolute reduction in relapse, therefore, was 5%, and the relative risk reduction was 17% with FEC/docetaxel. The disease-free survival rate was 78.3% vs 73.2% with FEC-only (P = .014 log-rank adjusted).
There were 100 deaths in the FEC/docetaxel arm (10%), compared with 135 deaths (13.5%) in the FEC-only arm. The overall survival rate, therefore, was 90.7% vs 86.7% (P = .017), representing a 23% relative risk reduction.
Dr. Roche pointed out that both therapies yielded very good outcomes. "At 5 years, approximately 90% of women with node-positive cancer are still alive, so FEC alone is also very effective. We are comparing two very good therapies," he said.
The significant improvement in disease-free survival and overall survival was "exclusively observed" in women aged 50 and older, Dr. Roche further reported. "For those under age 50, the outcomes were similar between the arms."
Clifford Hudis, MD, chief of the Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, commented, "It is provocative that the results for the age subsets are different from our usual experience. . . . This is a paradox, because the benefit was seen in a population that is traditionally less chemosensitive than younger patients."
But he added that he would be cautious about overemphasizing the differences according to age, especially when the findings are unexpected, and said he would not withhold this regimen from younger women, based on this study.
Both approaches were well tolerated. Hematologic toxicity was similar between the arms, except for a higher incidence of neutropenia among the FEC-only arm20.2% vs 10.9% (P < .001)and more febrile neutropenia on the FEC/docetaxel arm3.7% vs 7.2% (P = .032) (the majority of events occurred during cycles 4 to 6). Cardiac events occurred in 1.3% of the FEC-only arm and 0.4% of the FEC/docetaxel arm (P = .027). FEC/docetaxel was associated with more moderate-to-severe edema and nail problems, but less nausea and vomiting.
Peter Ravdin, MD, clinical professor of medical oncology, University of Texas Health Sciences Center, San Antonio, remarked, "This trial takes one of the best anthracycline-based regimens and substitutes the last three cycles with docetaxel. The study found a reduction in relapses and deaths, compared to what is already a good regimen. In fact, this looks as good as dose-dense therapy and other aggressive approaches, and the data at 5 years are more mature than what we have with dose-dense therapy. This challenges us as clinicians to re-examine whether we should use an adjuvant regimen that includes FEC."