Sequntial ACT better than concurrent TAC or AT

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Hi, folks.  If you haven't started chemo yet, and are choosing between TAC (all drugs at same time) and ACT (first AC then Taxane), this article suggests that ACT might be better.

Longer Therapy, Iatrogenic 
Amenorrhea, and Survival in Early Breast Cancer
N Engl J Med. 
2010 Jun 3;362(22):2122-2124, SM Swain, JH Jeong, CE Geyer Jr, JP 
Costantino, ER Pajon, L Fehrenbacher, JN Atkins, J Polikoff, VG Vogel, 
JK Erban, P Rastogi, RB Livingston, EA Perez, EP Mamounas, SR Land, PA 
Ganz, N Wolmark

ABSTRACT
In this study that enrolled more than
 5000 women with early-stage, node-positive, operable breast cancer, 
chemotherapy with sequential-ACT improved both DFS and OS when compared 
with four cycles of doxorubicin/docetaxel...

Background: 
Chemotherapy regimens that combine anthracyclines and taxanes result in 
improved disease-free and overall survival among women with operable 
lymph-node-positive breast cancer. The effectiveness of concurrent 
versus sequential regimens is not known.

Methods: We randomly 
assigned 5351 patients with operable, node-positive, early-stage breast 
cancer to receive four cycles of doxorubicin and cyclophosphamide 
followed by four cycles of docetaxel (sequential ACT); four cycles of 
doxorubicin and docetaxel (doxorubicin-docetaxel); or four cycles of 
doxorubicin, cyclophosphamide, and docetaxel (concurrent ACT). The 
primary aims were to examine whether concurrent ACT was more effective 
than sequential ACT and whether the doxorubicin-docetaxel regimen would 
be as effective as the concurrent-ACT regimen. The secondary aims were 
to assess toxic effects and to correlate amenorrhea with outcomes in 
premenopausal women.

Results: At a median follow-up of 73 months,
 overall survival was improved in the sequential-ACT group (8-year 
overall survival, 83%) as compared with the doxorubicin-docetaxel group 
(overall survival, 79%; hazard ratio for death, 0.83; P=0.03) and the 
concurrent-ACT group (overall survival, 79%; hazard ratio, 0.86; 
P=0.09). Disease-free survival was improved in the sequential-ACT group 
(8-year disease-free survival, 74%) as compared with the 
doxorubicin-docetaxel group (disease-free survival, 69%; hazard ratio 
for recurrence, a second malignant condition, or death, 0.80; P=0.001) 
and the concurrent-ACT group (disease-free survival, 69%; hazard ratio, 
0.83; P=0.01). The doxorubicin-docetaxel regimen showed noninferiority 
to the concurrent-ACT regimen for overall survival (hazard ratio, 0.96; 
95% confidence interval, 0.82 to 1.14). Overall survival was improved in
 patients with amenorrhea for 6 months or more across all treatment 
groups, independently of estrogen-receptor status.
Conclusion: 
Sequential ACT improved disease-free survival as compared with 
doxorubicin-docetaxel or concurrent ACT, and it improved overall 
survival as compared with doxorubicin-docetaxel. Amenorrhea was 
associated with improved survival regardless of the treatment and 
estrogen-receptor status.

Edited by dmwolf - Jun 21 2010 at 11:20pm