Taxol before AC, rather than the usual AC, then Taxol?

Chemotherapy Sequence Affects Early Breast Cancer Outcomes

Elsevier Global Medical News. 2011 Jan 7, B Jancin

SAN ANTONIO (EGMN) — The sequence in which paclitaxel and anthracyclines are given for treatment of early breast cancer makes a big difference in long-term outcomes.

That's the conclusion reached in what is believed to be the largest-ever retrospective study of the clinical impact of the sequencing of taxanes and anthracyclines. The study involved 3,010 early breast cancer patients who were treated during 1994-2009 and entered into the prospective online database at the University of Texas M.D. Anderson Cancer Center, Houston.

The clear winner was paclitaxel, followed by anthracycline-based therapy with 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide or 5-fluorouracil, epirubicin, and cyclophosphamide, Dr. Ricardo H. Alvarez reported at the San Antonio Breast Cancer Symposium.

Starting with paclitaxel rather than an anthracycline-first regimen led to better long-term results in the settings of adjuvant chemotherapy and primary systemic (or neoadjuvant) therapy.

The adjuvant chemotherapy analysis included 1,596 women, three-quarters of whom received paclitaxel followed by anthracyclines. The 5-year relapse-free survival rate with this regimen was 88.8%, compared with 79.5% when anthracyclines were followed by paclitaxel. The 10-year relapse-free survival rates were 81.8% and 73.5%, respectively.

Five-year overall survival was 93.1% with paclitaxel followed by anthracyclines, compared with 83.2% for the reverse. The 10-year overall survival rates were 83.9% and 65.6%, respectively.

In a multivariate analysis that was stratified for potential confounders, including age, clinical stage, hormone receptor status, tumor grade, and era of diagnosis, the anthracyclines-first sequence was associated with a 67% increased risk of relapse (P less than .0001) and a 2.5-fold greater risk of mortality (P = .001), according to Dr. Alvarez, a medical oncologist at M.D. Anderson.

Among 1,414 patients who underwent neoadjuvant therapy, the 5-year relapse-free survival rate was 79.0% with the paclitaxel-first regimen vs. 61.2% with the anthracyclines-first regimen. Ten-year relapse-free survival occurred in 61.7% and 50.5%, respectively, of these patients.

Overall survival was 84.2% and 66.2% at 5 and 10 years, respectively, in patients who received paclitaxel followed by anthracyclines, compared with 71.3% and 53.4% in those who got anthracyclines first.

In a multivariate analysis, the anthracyclines-followed-by-paclitaxel sequence of neoadjuvant chemotherapy was associated with an adjusted 49% higher risk of relapse (P = .01) and a nonsignificant 28% increase in risk of all-cause mortality (P = .17), compared with the paclitaxel-first strategy.

The mechanism that accounts for the increased efficacy of taxane-first regimens for treatment of breast cancer is unclear, according to Dr. Alvarez.