SWOG S0221: A phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer

George T. Budd, William E. Barlow, Halle C.F. Moore, Timothy J. Hobday, James A. Stewart, Claudine Isaacs, Muhammad Salim, Jonathan K. Cho, Kristine J. Rinn, Kathy S. Albain, Helen K. Chew, Gary V. Burton, Timothy D. Moore, Gordan Srkalovic, Bradley A. McGregor, Lawrence E. Flaherty, Robert B. Livingston, Danika L. Lew, Julie R. Gralow, Gabriel N. Hortobagyi

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Purpose: To determine the optimal dose and schedule of anthracycline and taxane administration as adjuvant therapy for early-stage breast cancer. Patients and Methods: A 2 × 2 factorial design was used to test two hypotheses: (1) that a novel continuous schedule of doxorubicin-cyclophosphamide was superior to six cycles of doxorubicin-cyclophosphamide once every 2 weeks and (2) that paclitaxel once per week was superior to six cycles of paclitaxel once every 2 weeks in patients with node-positive or high-risk node-negative early-stage breast cancer. With 3,250 patients, a disease-free survival (DFS) hazard ratio of 0.82 for each randomization could be detected with 90% power with two-sided α =.05 Overall survival (OS) was a secondary outcome Results Interim analyses crossed the futility boundaries for demonstrating superiority of both once-per-week regimens and once-every-2-weeks regimens. After a median follow-up of 6 years, a significant interaction developed between the two randomization factors (DFS P =.024; OS P = 010) in the 2,716 patients randomly assigned in the original design, which precluded interpretation of the two factors separately. Comparing all four arms showed a significant difference in OS (P = 040) but not in DFS (P =.11), with all treatments given once every 2 weeks associated with the highest OS. This difference in OS seemed confined to patients with hormone receptor-negative/human epidermal growth factor receptor 2 (HER2) -negative tumors (P =.067), with no differences seen with hormone receptor-positive/HER2-negative (P =.90) or HER2-positive tumors (P =.40) Conclusion: Patients achieved a similar DFS with any of these regimens. Subset analysis suggests the hypothesis that once-every-2-weeks dosing may be best for patients with hormone receptor-negative/HER2-negative tumors.

Original languageEnglish (US)
Pages (from-to)58-64
Number of pages7
JournalJournal of Clinical Oncology
Issue number1
StatePublished - Jan 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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