Epirubicin Cytoxan followed by Taxotere Herceptin for adjuvant terapy of breast cancer – pro

Since 1998, the standard of care for patients with node-positive breast cancer in the United States and other parts of the world has been treatment with doxorubicin and cyclophosphamide followed by the taxane paclitaxel. Herceptin is added for HER+ disease.  This treatment regimen was based on an intergroup study demonstrating that the addition of paclitaxel to doxorubicin and cyclophosphamide (AC) led to rates of disease-free survival of 70 percent and overall survival of 80 percent at five years, as compared with 65 percent and 77 percent, respectively, for doxorubicin and cyclophosphamide alone, with modest differences in the rate of toxic effects.

Because both docetaxel (Taxotere; Rhône-Pouleuc Rorer, Collegeville, PA) and paclitaxel have substantial non-cross-resistance with anthracyclines and therefore activity in anthracycline-resistant breast cancer, defining their roles in the adjuvant therapy of breast cancer is an area of great interest and active clinical investigation. The results of the adjuvant trials using docetaxel assume a particular importance because of the two taxanes in clinical use at this time, docetaxel may be the more active agent in the treatment of metastatic breast cancer, as demonstrated in the results from phase II and III randomized trials.

There are two substitutions to this standard in this case: Epirubicin for Adrimaycin and Taxoter for Taxol.

Based on the above studies, as well as phase II trials, 82 the NSABP B-30 study was designed to directly compare the sequential regimen of AC followed by docetaxel to the combination of doxorubicin plus docetaxel and to the triple combination of doxorubicin plus docetaxel plus cyclophosphamide. This trial was initiated in 1999 and has accrued more than 4,500 of the 5,300 patients needed. Final results are pending but docetaxela appears so far to be equivalent but perhaps slighly more toxic.

The Breast International Group 02-98 randomized trial tested the effect of incorporating docetaxel into anthracycline-based adjuvant chemotherapy and compared sequential vs concurrent administration of doxorubicin and docetaxel. Incorporating docetaxel into anthracycline-based therapy resulted in an improvement in DFS that was of borderline statistical significance. However, important differences may be related to doxorubicin and docetaxel scheduling, with sequential but not concurrent administration, appearing to produce better DFS than anthracycline-based chemotherapy.

Thus, Taxotere is acceptable to sustitue for Taxol. Herceptin is also now an standard of care part of the adjuvant regimen for node positive disease.

The remaining question is whether epirubicin can substitute for adriamycin, a similar but more cardiotoxic drug. and whether CE is as effective given after Taxotere rather as in most studies, in reverse sequence. It seems that such is the case based on substantial literature.


National Comprehensive Cancer Network (NCCN). Breast cancer. Clinical Practice Guidelines in Oncology — v2.2005. Jenkintown, PA: NCCN; 2005.

Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al.; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659-1672.
Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673-1684.

Ahluwalia M. S., Daw H. A., Noronha V., Martin M., Vogel C., the Breast Cancer International Research Group Adjuvant Docetaxel for Node-Positive Breast Cancer.
N Engl J Med 2005; 353:954-955, Sep 1, 2005

Adjuvant Chemotherapy With Sequential or Concurrent Anthracycline and Docetaxel: Breast International Group 02–98 Randomized Trial
Prudence Francis, John Crown, Angelo Di Leo, Marc Buyse, Ana Balil, Michael Andersson, Bo Nordenskjöld, Istvan Lang, Raimund Jakesz, Daniel Vorobiof, Jorge Gutiérrez, Guy van Hazel, Stella Dolci, Sophie Jamin, Belguendouz Bendahmane, Richard D. Gelber, Aron Goldhirsch, Monica Castiglione-Gertsch, Martine Piccart-Gebhart
On behalf of the BIG 02-98 Collaborative Group Journal of the National Cancer Institute
JNCI Journal of the National Cancer Institute 2008 100(2):121-133;

S. Gluck Adjuvant Chemotherapy for Early Breast Cancer: Optimal Use of Epirubicin
Oncologist, November 1, 2005; 10(10): 780 – 791.

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