(CHICAGO, IL) – Adding weekly paclitaxel to adjuvant FAC (5-fluorouacil, Adriamycin, cyclophosphamide) therapy offers a modest improvement in disease-free survival (DFS) for patients with high-risk, node-negative breast cancer, according to an efficacy study reported at the 2012 American Society of Clinical Oncology Annual Meeting.

Patients treated with adjuvant FAC followed by weekly paclitaxel (FAC+P) experienced a “small but significant improvement” in DFS vs. FAC alone, with manageable toxicity, said lead author Miguel Martín, MD, PhD, Spanish Breast Cancer Research Group and Hospital General Universitario Gregorio Marañón, Madrid, Spain.

In an earlier trial, adjuvant weekly paclitaxel following anthracyclines had been shown to improve the outcome of operable node-positive breast cancer patients, but most breast cancer patients are node-negative at the time of diagnosis, hence the potential benefits of weekly paclitaxel in this larger population had not yet been well-established, explained Dr. Martín. The primary endpoint of the study was DFS.

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Patients were randomly assigned to two study arms: 974 patients received 6 cycles of FAC (500/50/500mg/m2 every 3 weeks) and 951 received 4 cycles of FAC followed by weekly paclitaxel (100mg/m2 weekly) for 8 cycles.

The proportion of patients who were disease-free after a median follow-up of 63.3 months was 93% among patients in the FAC+P arm and 90% among FAC-only-arm patients (log-rank P-value=0.0432), for a 27% reduction in risk of DFS events (HR 0.733 [95% CI 0.542–0.992]; P=0.0441). The HR for overall survival was 0.766 (95% CI: 0.481–1.222).

Of the 100 patients who relapsed in the FAC group, 68 had breast cancer, 21 had a second primary malignancy, and 11 died; in the FAC+P group, 50 had breast cancer, 21 had a second primary malignancy, and 2 died.

Both regimens were well tolerated; FAC+P was associated with more Grade 3/4 sensory neuropathy (5.39% vs. 0%; P<0.00001), fatigue (7.93% vs. 3.4% (P<0.00001), infection (2.54% vs. 0.62%; P=0.00071), irregular menses (15.96% vs. 10.5%; P=0.00042), and thrombosis/embolism (1.06% vs. 0.10%; P=00468, which included one toxic death in cycle 7), whereas FAC was associated with more late cardiac toxicity: 3 deaths from cardiac ischemia/infections and 2 from arrhythmia, Dr. Martin said.