Common Breast Cancer Regimen Comes In Third


SAN ANTONIO — One of the most commonly used breast cancer chemotherapy regimens—the combination of doxorubicin and cyclophosphamide followed by paclitaxel—proved “significantly inferior” to two others in a major randomized trial, Dr. Margot Burnell said at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

The MA.21 study involved 2,104 women, from either Canada or the United States, with axillary lymph node-positive or high-risk node-negative operable breast cancer who were randomized to one of three 6-month intravenous chemotherapy regimens: doxorubicin and cyclophosphamide followed by paclitaxel, known as AC/T; another commonly used regimen consisting of cyclophosphamide, epirubicin, and fluorouracil (CEF); or 3 months of dose-dense epirubicin and cyclophosphamide followed by 3 months of paclitaxel (EC/T). (Dose-dense chemotherapy is delivered with briefer-than-standard intervals between doses.)

The hypothesis was that EC/T—the most recently developed and least widely used of the regimens—would prove superior.

An earlier trial in women with locally advanced breast cancer had established that 3 months of dose-dense EC was equivalent to 6 months of CEF, and the thinking was that tacking on 3 months of paclitaxel after EC would further enhance the dose-dense approach, explained Dr. Burnell, an oncologist who practices in St. John, N.B.

She presented a prespecified interim analysis showing that at a median 30.4 months, the primary study end point—recurrence-free survival—was significantly worse in the AC/T arm. (See table below.)

The AC/T arm also had more deaths, although this end point won't be formally analyzed until after another 2-3 years of follow-up.

In adjusted paired comparisons, patients in the AC/T arm were 49% more likely to have a recurrence than were those assigned to CEF, and 68% more likely to develop a recurrence than were those who received EC/T.

There was no significant difference in risk between the CEF and EC/T groups. Additional follow-up will be required to determine whether adding a taxane to dose-dense EC is worthwhile.

With regard to toxicities, patients on CEF or EC/T had substantially more febrile neutropenia than did those on AC/T. They also had more thromboembolic events, probably because of greater use of central lines.

Cardiotoxicity was similar across all three groups.

Neurotoxicity occurred primarily in conjunction with paclitaxel.

The trial was supported by the Canadian Cancer Society, the National Cancer Institute of Canada, the U.S. National Cancer Institute, Pfizer Inc., Bristol-Myers Squibb Co., Amgen Inc., Janssen-Ortho Inc., and Ortho Biotech Products L.P.


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