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Related Article: Original Article, N Engl J Med 2010 :362 ;2122 -2065 .
Over the past several decades, taxane-based chemotherapy regimens for breast cancer have evolved through a large number of randomized studies designed to detect modest improvements in patient outcome with changes in the dose, schedule, and agent or agents. Consequently, the choice of regimen remains confusing, even for the seasoned practitioner, let alone for a patient trying to make an informed decision. The National Surgical Adjuvant Breast and Bowel Project B-30 trial, reported on by Swain et al.1 in this issue of the Journal, is a good example of how clinical trials of chemotherapy in breast cancer are designed and performed.
This trial was developed to identify a short-course, taxane-based chemotherapy regimen for node-positive disease. The study compared three regimens: four cycles of doxorubicin, cyclophosphamide, and docetaxel (concurrent ACT), a similar 12-week regimen without cyclophosphamide (doxorubicin-docetaxel), and a 24-week regimen in which docetaxel was administered separately from the doxorubicin-cyclophosphamide combination (sequential ACT). The trial was powered to detect superiority of the 12-week, concurrent-ACT combination over sequential ACT on the theoretical basis that the triple combination would have synergistic activity.
However, the results provided support for the opposite conclusion. Both short-course regimens were less effective than the 24-week regimen. In absolute terms, sequential ACT was approximately 5 percentage points better for 8-year disease-free survival and approximately 4 percentage points better for overall survival. The results provide support for current practice, since the sequential-ACT regimen in this trial, or its paclitaxel-based equivalents, is standard therapy for node-positive disease. Some of these regimens already offer a shorter course of treatment. For example, the routine use of granulocyte colony-stimulating factor in the Cancer and Leukemia Group B (CALGB) 9741 trial (ClinicalTrials.gov number, NCT00003088) allowed eight cycles of sequential ACT to be given every 2 weeks (for a total of 16 weeks) as long as the taxane chosen was paclitaxel.2 The design of CALGB 9741 supported the principle of dose density, since the shorter regimens, otherwise identical for drug and dose, were more effective than the longer regimens. Thus, one of the main conclusions of the trial reported on by Swain et al. -- that a longer duration of treatment was better -- should not be considered...