Sixteen-week multidrug regimen versus cyclophosphamide, doxorubicin, and fluorouracil as adjuvant therapy for node-positive, receptor-negative breast cancer: an Intergroup study.
ABSTRACT The Intergroup conducted this breast cancer adjuvant trial to compare an investigational 16-week regimen with cyclophosphamide, doxorubicin, and fluorouracil (5-FU; CAF). The 16-week regimen features greater doxorubicin and 5-FU dose-intensity than CAF and improved scheduling of antimetabolites with sequential methotrexate and 5-FU, as well as infusion 5-FU.
A total of 646 node-positive, receptor-negative patients were randomly assigned to receive either the 1 6-week regimen or six cycles of CAF. Breast cancer outcomes included recurrence as well as disease-free and overall survival. Toxicity was evaluated by the Common Toxicity Criteria (CTC). Treatment-related quality of life was assessed by the Breast Chemotherapy Questionnaire (BCQ) before, during, and 4 months after treatment in 163 patients. The trial was designed to use one-sided tests of significance for power calculations, but is now reported with both one-sided and the traditional two-sided tests of significance.
At a median follow-up of 3.9 years, the estimated 4-year recurrence-free survival rate was 67.5% with the 16-week regimen versus 62.7% with CAF (P = .19, two-sided; P = .095, one-sided). The estimated 4-year survival rate was 78.1% with the 16-week regimen versus 71.4% with CAF (P = .10, two-sided; P = .05, one-sided). CAF produced significantly higher grades of leukopenia, granulocytopenia, and thrombocytopenia, as well as liver and cardiac toxicity, whereas the 16-week regimen produced significantly higher grades of anemia, nausea, stomatitis, and weight loss, as well as skin and neurotoxicity. There were three treatment-related deaths with CAF but none with the 16-week regimen. During treatment, quality of life declined significantly more with the 16-week regimen than CAF, but by 4 months posttreatment, there was no difference.
The 16-week regimen produced marginally better breast cancer outcomes than CAF with similar toxicity but a greater reduction in during-treatment quality of life. The 16-week regimen should not be used instead of a standard-dose regimen without careful consideration of the 16-week regimen's pros and cons, which include its complicated schedule. It should probably not be tested further, but its antimetabolite schedules and frequent drug administration (ie, dose density) should be considered in the development of new regimens.
SourceAvailable from: Amye J Tevaarwerk[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND: Population-based studies have shown improved survival for patients diagnosed with metastatic breast cancer over time, presumably because of the availability of new and more effective therapies. The objective of the current study was to determine whether survival improved for patients who developed distant recurrence of breast cancer after receiving adjuvant therapy. METHODS: Adjuvant chemotherapy trials coordinated by the Eastern Cooperative Oncology Group that accrued patients between 1978 and 2002 were reviewed. Survival after distant disease recurrence was estimated for progressive time periods, and adjusted for baseline covariates in a Cox proportional hazards model. RESULTS: Of the 13,785 patients who received adjuvant chemotherapy in 11 trials, 3447 (25%) developed distant disease recurrence; the median survival after recurrence was 20 months (95% confidence interval, 19 months-21 months). Factors associated with inferior survival included a shorter distant recurrence-free interval (DRFI), estrogen receptor-negative and progesterone receptor-negative disease, the number of positive axillary lymph nodes present at the time of diagnosis, and black race (P < .0001 for all). When the time period of recurrence was added to the model, it was not found to be significantly associated with survival for the general population with disease recurrence. Survival improved over time only in those patients with hormone receptor-negative disease with a DRFI ≤ 3 years, both among the 5 most recent and the entire trial data sets (P = .01 and P = .05, respectively). CONCLUSIONS: In contrast to reports from population-based studies, no general improvement in survival was observed over the last 30 years for patients who developed distant disease recurrence after adjuvant chemotherapy after adjusting for DRFI. Improved survival for patients with hormone receptor-negative disease with a short DRFI suggests a benefit from trastuzumab. Cancer 2012. © 2012 American Cancer Society.Cancer 10/2012; 119(6). DOI:10.1002/cncr.27819 · 4.90 Impact Factor
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ABSTRACT: The aim of our research is focused in elucidating the mechanisms by which the normal regulatory pathways coordinating centrosome duplication with cell cycle events may become uncoupled promoting breast cancer development, progression, chemoresistance and consequent poor outcome. The preliminary results reported in this grant suggest that the development and progression of breast cancer is a complex process involving the role of estrogens, growth factor signaling pathways and abrogation of the p53 protein leading to an inactivation of cell cycle checkpoints. We have demonstrated that although MCF-7 cells stable transfected with a dominant-negative p53 construct, maintain estrogen-dependent properties, the timing of centrosome duplication and cyclin/cdk complexes is deregulated following mitogen stimulation. Interestingly, over-expression of cyclin A plays a critical role in the development of centrosome amplification following hormone stimulation. We also have shown that genotoxic stress leads to centrosome amplification in MCF-7 breast cancer cells with mutant p53, but not in MCF-7 cells over-expressing oncoproteins in the EGF mitogen signaling pathway with wild-type p53 background. Our findings demonstrate that over-expression of EGF mitogen signaling proteins is not sufficient to induce centrosome amplification following genotoxic stress, conferring to p53 a key role in the control of centrosome homeostasis and genomic stability. They also suggest that chemotherapy agents inducing DNA damage may lead to the selection of resistant clones through centrosome amplification only in cells with mutant p53 regardless over-expression of the EGF signaling pathway.
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ABSTRACT: To review nursing research contributions and future opportunities for nurses in cooperative oncology group research in SWOG (formerly Southwest Oncology Group). Peer-reviewed journal articles, grant submissions, professional manuals, research policy reports, and meeting minutes. Nurses and nurse researchers have had active roles in SWOG research involving quality of life, symptom management, recruitment and adherence, and data quality. There are opportunities for nurses to make greater contributions to cooperative group research, particularly in cancer survivorship, health outcomes, and quality of life. Nursing science and evidence-based practice will be enhanced by conducting nursing research in the multi-site cooperative group setting.Seminars in Oncology Nursing 02/2014; 30(1):26-31. DOI:10.1016/j.soncn.2013.12.005