Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B- 22

Bernard Fisher, Stewart Anderson, D. Lawrence Wickerham, Arthur DeCillis, Nikolay Dimitrov, Eleftherios Mamounas, Norman Wolmark, Reginald Pugh, James N. Atkins, Frederick J. Meyers, Neil Abramson, Janet Wolter, Richard S. Bornstein, Lawrence Levy, Edward H. Romond, Vincent Caggiano, Manuel Grimaldi, Peter Jochimsen, Peter Deckers

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281 Scopus citations

Abstract

Purpose: The National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a randomized trial (B-22) to determine if intensifying but maintaining the total dose of cyclophosphamide (Cytoxan, Bristol-Myers Squibb Ontology, Princeton, NJ) in a doxorubicin (Adriamycin, Pharmacia, Kalamazoo, MI)-cyclophosphamide combination (AC), or if intensifying and increasing the total dose of cyclophosphamide improves the outcome of women with primary breast cancer and positive axillary nodes. Patients and Methods: Patients (N = 2,305) were randomized to receive either four courses of standard AC therapy (group 1); intensified therapy, in which the same total dose of cyclophosphamide was administered in two courses (group 2); or intensified and increased therapy, in which the total dose of cyclophosphamide was doubled (group 3). The dose and intensity of doxorubicin were similar in all groups. Disease-free survival (DFS) and overall survival were determined using life-table estimates. Results: There was no significant difference in DFS (P = .30) or overall survival (P = .95) among the groups through 5 years. At 5 years, the DFS of women in group 1 was similar to that of women in group 2 (62% v 60%, respectively; P = .43) and to that of women in group 3 (62% v 64%, respectively; P = .59). The 5-year survival of women in group 1 was similar to that of women in group 2 (78% v 77%, respectively; P = .86) and to that of women in group 3 (78% v 77%, respectively; P = .82). Grade 4 toxicity increased in groups 2 and 3. Failure to note a difference in outcome among the groups was unrelated to either differences in amount and intensity of cyclophosphamide or to dose delays and intervals between courses of therapy. Conclusion: Intensifying or intensifying and increasing the total dose of cyclophosphamide failed to significantly improve either DFS or overall survival in any group. It was concluded that, outside of a clinical trial, dose-intensification of cyclophosphamide in an AC combination represents inappropriate therapy for women with primary breast cancer.

Original languageEnglish (US)
Pages (from-to)1858-1869
Number of pages12
JournalJournal of Clinical Oncology
Volume15
Issue number5
StatePublished - May 1997

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Fisher, B., Anderson, S., Wickerham, D. L., DeCillis, A., Dimitrov, N., Mamounas, E., Wolmark, N., Pugh, R., Atkins, J. N., Meyers, F. J., Abramson, N., Wolter, J., Bornstein, R. S., Levy, L., Romond, E. H., Caggiano, V., Grimaldi, M., Jochimsen, P., & Deckers, P. (1997). Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B- 22. Journal of Clinical Oncology, 15(5), 1858-1869.