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Journal of Clinical Oncology, Vol 22, No 4 (February 15), 2004: pp. 749-a-780 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.99.114
Dose-Dense Chemotherapy As Adjuvant Treatment for Breast CancerSouth Shore Hematology-Oncology Associates, Rockville Centre, NY To the Editor: Citron et al [1] present the Intergroup C9741/Cancer and Leukemia Group B Trial 9741 as a 2 x 2 factorial design. Their interpretation assumes similarity of the treatments in each individual category (ie, dose-dense, non–dose-dense, sequential, and concurrent). This assumption is flawed. Of special concern is the sequential every-3-week regimen, which would be expected to be inferior to the other regimens. The failure to show a statistically significant interaction between dose density and sequence of treatment is not reassuring—this only means that we cannot be 95% sure that there is no interaction, a far cry from proving that there is none. A more appropriate analysis would be to compare each treatment regimen with the others. The authors' statement that "this study is not designed for formal comparisons among the arms" is specious. Although the authors may not have intended such an analysis, there is nothing to prevent them from carrying it out. The reader may appropriately use his or her own estimates of expected probabilities to apply Bayes' theorem to subgroup analyses and thereby determine the posterior probability that the results may be trusted [2]. Inspection of Figure 4B of the Citron et al [1] article suggests that the only difference likely to be significant is the poorer survival in the sequential every-3-week group compared to the other groups, a concern raised by Piccart-Gebhart [3]. The authors should report the survival difference between the sequential treatments given every 3 weeks versus every 2 weeks (regimens III and IV). If a survival difference between these treatments cannot be proven, the higher-cost dose-dense regimen cannot be recommended. Rather than proving that dose-dense therapy offers a survival advantage over standard every-3-week treatment, the authors may have once again proven that suboptimal chemotherapy yields suboptimal results [4]. Author's Disclosures of Potential Conflicts of Interest The author indicated no potential conflicts of interest. REFERENCES 1. Citron ML, Berry DA, Cirrincione C, et al: Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 21:1421-1439, 2003 2. Atkins CD: A clinician's view of statistics. J Gen Intern Med 12:500-504, 1997[Medline]
3. Piccart-Gebhart MJ: Mathematics and oncology: A match for life? J Clin Oncol 21:1425-1428, 2003
4. Wood WC, Budman DR, Korzun AH, et al: Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med 330:1253-1259, 1994 Related Article
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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