Taxotere Adriamycin Cytoxan for adjuvant therapy 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. The next step was the development of the TAC regimen, in which a taxane is given concurrently with AC.

TAC is clearly effective in node positive women. Adjuvant chemotherapy with docetaxel reduced the risk of death from node-positive early-stage breast cancer by 30% at 55 months of follow-up in a major phase III trial. The combination of docetaxel (Taxotere), doxorubicin (Adriamycin), and cyclophosphomide (Cytoxan) (TAC) also cut the risk of relapse by 28% compared with the standard three-drug regimen of 5-fluorouracil, doxorubicin, and cyclophosphomide (FAC).

The Breast Cancer International Research Group (BCIRG) conducted the trial known as BCIRG 001. The randomized study enrolled 1,491 women in 20 countries from June 1997 to June 1999. The new data are based on 55-month follow-up from 92% of participants. Disease-free survival reached 75% for the women receiving TAC vs. 68% for those receiving FAC. This translated into a hazard ratio of 0.72 (P = .0010). Overall survival at five years was 81% for the FAC cohort compared with 87% for the women receiving TAC (hazard ratio, 0.70; P = .0080). Subgroup analyses showed relapse rates decreased 27% in estrogen receptor–positive women and 34% in those who were estrogen receptor–negative. While women with one to three nodes fared better than those with four or more, both benefited; the hazard ratios were 0.61 (P = .0009) for the former and 0.82 (P = .1629) for the latter.
Patients with HER2-neu amplification also did better on TAC. The hazard ratio for HER2-positive patients receiving TAC was 0.61 (P = .0118) and for HER2-negative patients it was 0.76 (P = .0380). The only group that did not show significantly better outcomes on TAC compared to FAC was women with four or more positive lymph nodes. Among these participants, there was a trend toward superior results with TAC vs. FAC, but it did not reach statistical significance.

The absolute benefit in patients with node-negative disease may be much smaller and this may not outweigh the expected increase in toxicity. Martin et al. reported on the results of a randomized adjuvant trial comparing TAC with FAC for high-risk N0 breast cancer patients, the GEICAM 9805 trial. Comparisons are reported for toxicity and quality of life, not for efficacy, as follow-up time is still too short. After a protocol amendment, patients on the TAC arm received primary granulocyte colony-stimulating factor (G-CSF) prophylaxis, whereas before the amendment, only secondary G-CSF prophylaxis was allowed or even mandatory after an episode of febrile neutropenia. Unfortunately the report centered only on toxicity and we are still awaiting publication of this important study.

For node negative women, guidelines recommend: For premenopausal women at average to high risk, but whose tumors are hormonally responsive, ovarian ablation and tamoxifen, chemotherapy and tamoxifen, tamoxifen alone, or ovarian ablation alone can be considered standard therapy. Node-negative and premenopausal women with hormone-unresponsive cancer should be offered chemotherapy with AC, CMF, or cyclophosphamide-adriamycin-fluorouracil (CAF).

Other guidelines, however, NCCN, for example, are not as stringent on assigning specific regimens to either node+ or node negative group.

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

Breast Cancer Disease Site Group. Adjuvant systemic therapy for node-negative breast cancer [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2003 May 1 [online update]. 22 p. (Practice guideline report; no. 1-8). [79 references], breast cancer

Martin M, Lluch A, Segui M et al. Toxicity and health-related quality of life in breast cancer patients receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5-fluorouracil, doxorubicin and cyclophosphamide (FAC): impact of adding primary prophylactic granulocyte-colony stimulating factor to the TAC regimen. Ann Oncol 2006; 17: 1205–1212.

Participate in our Forums

To ask questions or participate in a discussion, please visit our Forums. You must LOGIN to participate.

Help Us Help Others

You can become a Site Sponsor. Or you may wish to support our work with a Donation.

Focused Articles For You

Lay Portal