The evidence supporting this protocol is provided by a randomised phase lll trial (TAX 316) by Martin et alr involving 1491 patients with axillary node-positive breast cancer who were randomised to 6 cycles of TAC (docetaxel, doxorubicin, cyclophosphamide) or FAC ( fluorouracil, doxorubicin, cyclophosphamide) as adjuvant treatment post surgery.
The study enrolled patients between 1997 and 1999 from 20 countries. In total 1480 patients (744 TAC and 736 FAC) received treatment and were included in the safety data. The primary end point was disease free survival (DFS) and the median follow up was 55 months.
TAC patients received ciprofloxacin as supportive care on days 5 to 14 of each treatment cycle. 70% of patients enrolled in this study were ER positive. Randomisation was stratified according to institution and the number of axillary lymph nodes (1 to 3 vs 4 or greater).
The TAX 316 trial showed there was a statistically significant difference in both DFS (HR 0.72, 95% CI 0.59 to 0.88, p=0.001) and OS (HR 0.70, 95% CI 0.53 to 0.91, p=0.008) favouring TAC over FAC. The estimated rates of disease free survival at five years were 75% with TAC and 68% with FAC and the overall survival estimates at 5 years were 87% with TAC and 81% with FAC.
Survival rates in the two study groupsr
© New England Journal of Medicine 2005
TAC is more toxic than FAC chemotherapy. Of the TAC group 36% (268/744) of patients developed serious treatment related adverse events compared with 9.2% (67/736) in the FAC arm. The incidence of grade 3/4 adverse events was also higher with TAC (10.2% vs 4.9%). Overall 91.3% of patients completed 6 cycles of TAC and 96.6% completed FAC. TAC was associated with more frequent febrile neutropenia, infection, long-term amenorrhoea, alopecia, peripheral oedema, neurosensory effects and cardiac failure. No deaths occurred as a result of infection. 3 patients developed secondary haematologic cancers (2 in TAC group and 1 in FAC group).r
|Adverse events* r
*Grade 3 or 4 adverse events (except febrile neutropenia - all grades)