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Sequntial ACT better than concurrent TAC or AT

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dmwolf View Drop Down
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    Posted: Jun 21 2010 at 11:19pm
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

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
DX 2/08@43 stg II IDC; gr2,0 nodes. Neoadj chemo, first ACx2 (fail) then CarboTaxotereX6(better). Lump, Rads done 11/08; Clodronate. False alarm queen: PetCT lung & TM marker. NED. PBM w/recon 9/10.
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