What is the Best Way to Administer Chemotherapy in Breast Cancer Patients?

The National Cancer Institute’s Breast Intergroup INT C9741 and CALGB 9741 trial published in 2003:
- Evaluated 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 (2 weeks vs. 3 weeks) and treatment sequence (concurrent versus sequential)
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 four 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

1. 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.

2. Orzano JA, Swain SM. Concepts and clinical trials of dose-dense chemotherapy for breast cancer. Clin Breast Cancer. 2005;6(5):402-411