Dose and Dose Intensity of Adjuvant Chemotherapy for Stage II, Node-Positive Breast Carcinoma

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Abstract
Adjuvant chemotherapy is widely used for breast cancer and is known to extend survival. Some clinicians seek a greater survival benefit by increasing the intensity of the dose, whereas others lower it to diminish toxicity. The Cancer and Leukemia Group B (CALGB) conducted a randomized trial of different levels of doses and dose intensity (dose per unit of time) of adjuvant chemotherapy in 1572 women with node-positive, stage II breast cancer who were assigned to three treatment groups. One group received 400 mg of cyclophosphamide per square meter of body-surface area and 40 mg of doxorubicin per square meter once every 28 days and 400 mg of fluorouracil per square meter twice every 28 days, for six cycles. Another group received 50 percent higher doses of the three drugs (600 mg, 60 mg, and 600 mg, respectively) but for only four cycles, so that the total dose was identical in these two groups but the dose intensity was higher in the second. The third group of women received half the total dose used in the other two groups and at half the dose intensity used in the second group. After a median of 3.4 years of follow-up, the women treated with a high or moderate dose intensity had significantly longer disease-free survival (P<0.001) and overall survival (P = 0.004) than those treated with a low dose intensity, in three-way log-rank comparisons. However, the difference in survival between the two groups treated with a moderate or high dose intensity was not significant. These results are consistent with either a dose-response effect or a threshold level of the dose or dose intensity. The doses of chemotherapy used to treat breast cancer, especially early breast cancer, should not be reduced if the maximal benefit is to be achieved. .