Dose Dense TAC – pro

Lay SUmmary: Dose dense TAC is being studied.

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 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. This regimen was first administered on a schedule of once every three weeks and then, more recently, once every two weeks, after a comparative trial demonstrated improved efficacy (a 7 percent absolute improvement in disease-free survival and a 2 percent improvement in overall survival at three years) with the schedule involving more frequent administration (referred to as dose-dense therapy). However, dose dense TAC is only now being tested.

The approach of dose dense TAC + Herceptin warrants a discussion of several points. First, what is the status of dose dense TAC chemotherapy? Second, is the agressive approach justified?

Leaving the second question aside, the fact is that dose dense TAC is currently in a phase III cinical trial. It is now widely agreed that every three week TAC is equivalent in effectiveness of dose dense (every two week) CA = Taxol. Prelimiary results of the dose dense approach were presented in 2007 ASCO, confirming tolerabilty but without information of effectiveness. This study shows that DD TCA plus G-CSF has comparable toxicity profile with standard TCA regimen with shorter treatment period. The study is ongoing for efectiveness and the DD TAC is the research arm – investigational

S. Z. Latifzadeh, M. Salimi, M. Naghnaeian, V. Entezari Dose-dense (DD) two-weekly docetaxel/doxorubicin/cyclophosphamide (TAC) with G-CSF support compared to standard adjuvant TAC in breast cancer patients.  Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 11052

Marc L. Citron, Donald A. Berry, Constance Cirrincione, Clifford Hudis, Eric P. Winer, William J. Gradishar, Nancy E. Davidson, Silvana Martino, Robert Livingston, James N. Ingle, Edith A. Perez, John Carpenter, David Hurd, James F. Holland, Barbara L. Smith, Carolyn I. Sartor, Eleanor H. Leung, Jeffrey Abrams, Richard L. Schilsky, Hyman B. Muss, Larry Norton Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741 Journal of Clinical Oncology, Vol 21, Issue 8 (April), 2003: 1431-1439

Edith A. Perez, M.D.  TAC — A New Standard in Adjuvant Therapy for Breast Cancer? NEJM Volume 352:2346-2348  June 2, 2005  Number 22

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