The National Cancer Institute’s Breast Intergroup INT C9741 and CALGB 9741 Trial

  • Published in 2003 the evaluation of combination chemotherapy for breast cancer:
    • Given by both dose dense and sequential therapy
    • The goal of the study was to evaluate the best way to administer the chemotherapy regimen:
      • Doxorubicin (A), cyclophosphamide (C) followed by paclitaxel (T)
    • The study assessed chemotherapy administration in:
      • A dose dense fashion:
        • Two weeks vs. three weeks
      • Treatment sequence:
        • Concurrent versus sequential
    • The findings of the study showed:
      • That dose density improved clinical outcomes significantly
      • Sequential chemotherapy was as effective as concurrent chemotherapy:
        • But required a longer time period of administration
  • Dose-dense chemotherapy:
    • Refers to decreasing the interval between cycles of treatment without the need of increasing doses and toxicity
  • Sequential therapy:
    • Refers to the administration of treatments one at a time rather than concurrently
  • National Cancer Institute’s Breast Intergroup INT C9741 and CALGB 9741 trial:
    • Was a prospective, randomized trial designed to study adjuvant chemotherapy treatment regimens:
      • In women with axillary node-positive breast cancer conducted from September 1997 to March 1999
    • Doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) were chosen for this study
    • Using a 2 x 2 factorial design, patients were assigned to receive one of the following 4 regimens:
      • Sequential A then C followed by T x 4 cycles every 3 weeks
      • Dose-dense, sequential A then C then T x 4 cycles every 2 weeks with filgrastim
      • Concurrent AC x 4 cycles followed by T x 4 cycles every 3 weeks
      • Dose-dense, concurrent AC x 4 cycles followed by T x 4 cycles every 2 weeks with filgrastim
  • Results showed that:
    • Dose-dense treatment improved the primary endpoints of:
      • Disease-free survival (DFS) and overall survival (OS):
        • Four-year DFS was 82% for dose-dense regimens and 75% for other groups (risk ratio, 0.74, P=0.01)
        • Three-year OS was 92% for dose-dense regimens and 90% in other groups (risk ratio, 0.69, P=0.013)
      • There was no difference in either DFS or OS:
        • Between the concurrent and sequential schedules
      • Severe neutropenia:
        • Was less common in patients who received the dose-dense regimens
      • As a result of this study:
        • Dose-dense and concurrent AC chemotherapy has become one of the standard components of breast cancer therapy
  • References:
    • Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, 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.2003;21(8):1431-1439.
    • Orzano JA, Swain SM. Concepts and clinical trials of dose-dense chemotherapy for breast cancer. Clin Breast Cancer. 2005;6(5):402-411

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