Despite improvements in disease-free and overall survival resulting from the use of adjuvant chemotherapy in patients with lymph node-positive breast cancer, a significant number of patients develop tumor recurrence and die from the disease. Therefore, there is a need to develop new treatment regimens that combine active drugs for the treatment of such patients and to test alternative schedules and agents.I am very actively involved with the NSABP and am the Protocol Chair for NSABP B30. The primary aims of this Phase III multinational trial are 1) to determine whether four cycles of post-operative doxorubicin (A), docetaxel (T), and cyclophosphamide (C) administered concurrently will more effectively prolong disease-free survival and overall survival of patients with lymph node-positive breast cancer than will 4 cycles of AC followed by 4 cycles of T, and 2) to determine whether 4 cycles of AT is at least as efficacious as the above two regimens. The rationale for the design of the study was the significant efficacy of docetaxel in patients withmetastatic breast cancer and the improved activity when used in combination with anthracyclines. The hypothesis is that concurrent combination with an active taxane is more important than the sequence or duration of therapy. The second hypothesis for the study is that cyclophosphamide is not essential for a survival benefit when used in combination with the two most active agents for breast cancer. The standard arm for this study is the AC followed by T arm because it was the experimental arm for the NSABP B27 study. The secondary aims of the study are to compare toxicities, to examine differences in amenorrhea in premenopausal women in each treatment arm and its relationship to symptoms, quality of life (QOL), disease-free survival and overall survival, and finally to compare the quality of life among patients in each of the three treatment arms.Ovarian damage is considered the most significant long-term sequela of adjuvant chemotherapy in premenopausal breast cancer survivors, and alkylating agents such as cyclophosphamide are often the cause of ovarian dysfunction. Furthermore, drug-induced amenorrhea may be a favorable prognostic factor in patients with breast cancer, although this is controversial. NSABP B-30 will compare the incidence of amenorrhea in each treatment arm of the study and will assess the association of amenorrhea with symptoms and quality of life. (Because the AT arm does not include cyclophosphamide, there may be less ovarian dysfunction with this regimen.) Documenting menstrual history in women participating in this protocol will provide a unique opportunity to assess the effect of induced menopause on disease-free and overall survival. A menstrual history study, which included a baseline and follow-up questionnaires at cycle 4, and at 6, 12, 18, and 24 months, was implemented in this trial. QOL assessments are an attempt to measure and scientifically analyze the impact of a disease and its treatment on patients' perception of their well-being. Studies have shown that, at the end of primary treatment for breast cancer, women report decreased physical functioning after chemotherapy. QOL will be assessed in NSABP B-30 by Functional Assessment of Cancer Therapy - Breast (FACT-B), Treatment-Specific Symptom Checklist, Vitality Scale (SF -36) and Quality of Life Rating Scale at the same time points as those for the menstrual history study. QOL assessment can be helpful in weighing the risk and benefits of treatment options, particularly when differences in disease-free and overall survival among the treatment options are small. The NSABP B-30 study began accrual in March 1999 and completed accrual of 5351 patients in March 2004. The expected reporting of the results is in 2007. There were 610 patients included in a preliminary report of the menstrual history study at the American Society of Clinical Oncology meeting.
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