A key current issue in ongoing treatment trials is defining the role of adjuvant taxanes, including selection of patients, choice of paclitaxel versus docetaxel and optimal scheduling. Recent phase III randomized trial data demonstrating a survival benefit to capecitabine/docetaxel in metastatic disease has led to new trials looking at this combination in the adjuvant setting. The 2000 NIH Consensus statement noted the small but statistically significant advantage conferred by anthracycline-containing regimens, but concluded that the optimal anthracycline-containing regimen has not been identified. The statement further noted that chemotherapy is generally offered to women with tumors over one centimeter, but in women with node-negative tumors under one centimeter, treatment should be individualized, as subsets of these patients have an excellent prognosis.

ADJUVANT TAXANES

It is necessary to wait for future results of ongoing trials before pronouncing judgment on the value of taxanes in the adjuvant setting. It is also necessary to better define the population most likely to benefit from therapies of longer duration, intensification and multiple regimens. It no longer is reasonable to judge all breast cancer patients as having equal probability of benefit from a given therapy. That was a paradigm that worked well when adjuvant chemotherapy for breast cancer was in its infancy and little was known about the molecular heterogeneity of breast cancer. It is now of critical importance to design trials with the aid of molecular tumor profiles with potential predictive value to prospectively identify the subgroup most likely to benefit from the addition to therapy of taxanes and other new drugs.

—Martine J Piccart, MD, PhD et al. NIH Consensus Conference 2000.

ADJUVANT THERAPY FOR LOW-RISK PATIENTS

Sometimes we neglect using some fairly well-established, reproducible prognostic factors. The SEER data and the American College of Surgeons’ National Cancer Database cannot reliably identify a subset of node-negative patients with tumors under a centimeter with a long-term survival of less than 90%. If physicians look at old consensus guidelines and just go in lock-step with the greater-than-1-centimeter number, they might potentially overtreat some patients by using chemotherapy.

—Monica Morrow, MD

FUTURE TRIALS LOOKING AT DOCETAXEL-CAPECITABINE

In the adjuvant setting, we’d like to look at a comparison of AC versus docetaxel-capecitabine in node-negative or ER/PR-positive, node-positive breast cancer. Another research issue is that as the role of the taxanes is better defined in the adjuvant setting — particularly in patients with ER-negative tumors — the obvious thought is to add capecitabine in with the taxane to see if you can save more lives. And I would guess you probably could, if you can define the subset of women who will benefit from taxanes in the adjuvant setting.

—Joyce O’Shaughnessy, MD

CAPECITABINE-DOCETAXEL: IMPLICATIONS FOR THE ADJUVANT SETTING

The capecitabine-docetaxel study points towards the adjuvant situation where we are already using a lot of taxanes. With the right dose, adding capecitabine may not add very much toxicity and may give more of an anti-tumor effect. The metastatic setting has always been the testing ground for adjuvant regimens. And at least now, we have a solid scientific lead to potentially plug into adjuvant treatment.

E-1199: PHASE III STUDY OF DOXORUBICIN AND CYCLOPHOSPHAMIDE FOLLOWED BY PACLITAXEL OR DOCETAXEL IN WOMEN WITH NODE-POSITIVE OR HIGH-RISK NODE-NEGATIVE STAGE II OR IIIA BREAST CANCER OPEN PROTOCOL PROJECTED ACCRUAL: A total of 5,000 patients will be accrued within 1.27 years.   NSABP B-30;CTSU: PHASE III RANDOMIZED STUDY OF ADJUVANT DOXORUBICIN AND CYCLOPHOSPHAMIDE FOLLOWED BY DOCETAXEL VERSUS DOXORUBICIN AND DOCETAXEL VERSUS DOXORUBICIN, DOCETAXEL AND CYCLOPHOSPHAMIDE IN WOMEN WITH BREAST CANCER AND POSITIVE AXILLARY LYMPH NODES OPEN PROTOCOL PROJECTED ACCRUAL :A total of 4,000 patients will be accrued within 3 years. T= Docetaxel A= Doxorubicin C= Cyclophosphamide   NATIONAL CANCER INSTITUTE OF CANADA MA.21 TRIAL: PHASE III RANDOMIZED STUDY OF ADJUVANT CYCLOPHOSPHAMIDE, EPIRUBICIN AND FLUOROURACIL VERSUS CYCLOPHOSPHAMIDE, EPIRUBICIN, FILGRASTIM (G-CSF) AND EPOETIN ALFA FOLLOWED BY PACLITAXEL VERSUS CYCLOPHOSPHAMIDE AND DOXORUBICIN FOLLOWED BY PACLITAXEL IN PREMENOPAUSAL OR EARLY POSTMENOPAUSAL WOMEN WITH PREVIOUSLY RESECTED NODE-POSITIVE OR HIGH-RISK NODE-NEGATIVE STAGE I-IIIA BREAST CANCER OPEN PROTOCOL T=paclitaxel     What adjuvant chemotherapy, if any, would you recommend for the following women with ER-positive, HER2-negative breast cancer? O N C O L O G I S T S

Early Breast Cancer Trialists’ Collaborative Group. Polychemotherapy for early breast cancer: An overview of the randomised trials. Lancet 1998;352(9132):930-42. Abstract

Hortobagyi GN. Progress in systemic chemotherapy of primary breast cancer: An overview. J Natl Cancer Inst Monogr 2001;30:72-79. Abstract

Morrow M, Krontiras H. Who should not receive chemotherapy? Data from American databases and trials. Cancer Inst Monogr 2001;30:109-113. Abstract

Nabholtz JM et al. Chemotherapy of breast cancer: Are the taxanes going to change the natural history of breast cancer? Expert Op in Pharmacother 2000;1:187-206. Abstract

Norton L. Theoretical concepts and the emerging role of taxanes in adjuvant therapy. Oncologist 2001;6 Suppl 3:30-5. Abstract

Piccart MJ et al. Taxanes in the adjuvant treatment of breast cancer: Why not yet? J Natl Cancer Inst Monogr 2001;30:88-95. Abstract

Vukeja SJ et al. Xeloda (capecitabine) plus docetaxel combination therapy in locally advanced/metastatic breast cancer: Latest results. Breast Cancer Res Treat 2001. Abstract

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