Dose-intense, dose-dense (F)AC+G adjuvant chemotherapy has excellent event-free survival in high-risk patients with 4-9 involved axillary nodes

Following the seminal suggestion of Hryniuk of improved outcomes with drug schedules achieving higher dose intensity [DI], we have pursued a series of pilot studies and report here on two using weekly doxorubicin [A] at 20-24 mg/m2, daily oral cyclophosphamide [C] at 60 mg/m2, scheduled G-CSF (filgrastim) [G] at 5 μg/kg (days 2-7 ea. week) given to 37 patients [pts] with median age of 41 (23-62). Because A was given weekly and C daily, this regimen is also dose dense. 5-FU [F] was given to the initial 17 pts (FAC+G), stopped because of hand-foot and because NSABP AC had become a national standard. The remainder received AC+G at the higher A dose. Pts had stage II or IIIA disease, 12/25 negative for both ER and PR, 13/29 positive for HER-2/neu overexpression. There was one admission for febrile neutropenia. Median follow-up is 49 months. Planned therapy was to a cumulative dose of A of 480 mg/m2. DI and toxicity are for all pts. For 21 pts who received no additional chemotherapy (FAC+G, 14/17, AC+G, 7/20), disease-free survival is 80%, with overall survival of 86%. This compares with DFS and OS for pts with 4-9 involved nodes reported by Hudis with Memorial's dose-dense AC of 64 and 70%, respectively [JCO, 1999 17(4): 1118-1126]. FAC+G AC+G Number 17 20 Median weeks Rx 25 19 Delivered DI, A 18.1 21.5 Delivered DI, C 380 372 Delivered DI, F 256 - Neutropenia grade III/IV 2/2 5/0 Thrombocytopenia grade III, IV 0 0 Anemia requiring transfusion 3 4 Anemia requiring Epo 6 6 Nausea grade III/IV 3/0 1/0 Vomiting grade III/IV 1/0 1/0 Diarrhea grade III/IV 0/1 0/0 Stomatitis grade III/IV 2/0 0/0 Hand/foot grade III/IV 2/0 2/0 Median follow-up (months) 65 42.