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

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Authors: Budd, G. T.; Barlow, W. E.; Moore, H. C.; Hobday, T. J.; Stewart, J. A.; Isaacs, C; Salim, M; Cho, J. K.; Rinn, K. J.; Albain, K. S.; Chew, H. K.; Burton, G. V.; Moore, T. D.; Srkalovic, G.; McGregor, B. A.; Flaherty, L. E.; Livingston, R. B.; Lew, D. L.; Gralow, J. R.; Hortobagyi, G. N.
Article Title: SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer
Abstract: 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 x 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 alpha = .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.
Journal Title: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume: 33
Issue: 1
ISSN: 1527-7755; 0732-183X
Publisher: by American Society of Clinical Oncology  
Journal Place: United States
Date Published: 2015
Start Page: 58
End Page: 64
Language: eng
DOI/URL:

10.1200/JCO.2014.56.3296
Notes: LR: 20150113; CI: (c) 2014; GR: 015469/PHS HHS/United States; GR: 021039/PHS HHS/United States; GR: CA04919/CA/NCI NIH HHS/United States; GR: CA11083/CA/NCI NIH HHS/United States; GR: CA12644/CA/NCI NIH HHS/United States; GR: CA128567/CA/NCI NIH HHS/United States; GR: CA13612/CA/NCI NIH HHS/United States; GR: CA14028/CA/NCI NIH HHS/United States; GR: CA20319/CA/NCI NIH HHS/United States; GR: CA21076/CA/NCI NIH HHS/United States; GR: CA21115/CA/NCI NIH HHS/United States; GR: CA22433/CA/NCI NIH HHS/United States; GR: CA25224/CA/NCI NIH HHS/United States; GR: CA27057/CA/NCI NIH HHS/United States; GR: CA32102/CA/NCI NIH HHS/United States; GR: CA35090/CA/NCI NIH HHS/United States; GR: CA35119/CA/NCI NIH HHS/United States; GR: CA35128/CA/NCI NIH HHS/United States; GR: CA35176/CA/NCI NIH HHS/United States; GR: CA35178/CA/NCI NIH HHS/United States; GR: CA35261/CA/NCI NIH HHS/United States; GR: CA35262/CA/NCI NIH HHS/United States; GR: CA35281/CA/NCI NIH HHS/United States; GR: CA35431/CA/NCI NIH HHS/United States; GR: CA37981/CA/NCI NIH HHS/United States; GR: CA38926/CA/NCI NIH HHS/United States; GR: CA42777/CA/NCI NIH HHS/United States; GR: CA45377/CA/NCI NIH HHS/United States; GR: CA45450/CA/NCI NIH HHS/United States; GR: CA45461/CA/NCI NIH HHS/United States; GR: CA45560/CA/NCI NIH HHS/United States; GR: CA45807/CA/NCI NIH HHS/United States; GR: CA45808/CA/NCI NIH HHS/United States; GR: CA46282/CA/NCI NIH HHS/United States; GR: CA46368/CA/NCI NIH HHS/United States; GR: CA46441/CA/NCI NIH HHS/United States; GR: CA52654/CA/NCI NIH HHS/United States; GR: CA58416/CA/NCI NIH HHS/United States; GR: CA58658/CA/NCI NIH HHS/United States; GR: CA58861/CA/NCI NIH HHS/United States; GR: CA58882/CA/NCI NIH HHS/United States; GR: CA63844/CA/NCI NIH HHS/United States; GR: CA63845/CA/NCI NIH HHS/United States; GR: CA63848/CA/NCI NIH HHS/United States; GR: CA67575/CA/NCI NIH HHS/United States; GR: CA67663/CA/NCI NIH HHS/United States; GR: CA68183/CA/NCI NIH HHS/United States; GR: CA74647/CA/NCI NIH HHS/United States; GR: CA76132/CA/NCI NIH HHS/United States; GR: CA76447/CA/NCI NIH HHS/United States; GR: CA77202/CA/NCI NIH HHS/United States; GR: CA77597/CA/NCI NIH HHS/United States; GR: CA86780/CA/NCI NIH HHS/United States; GR: CA95860/CA/NCI NIH HHS/United States; GR: CCSRI15469/PHS HHS/United States; GR: U10 CA038926/CA/NCI NIH HHS/United States; GR: U10 CA180819/CA/NCI NIH HHS/United States; GR: U10 CA180888/CA/NCI NIH HHS/United States; JID: 8309333; 33069-62-4 (Paclitaxel); 80168379AG (Doxorubicin); 8N3DW7272P (Cyclophosphamide); OID: NLM: PMC4268253 [Available on 01/01/16]; PMCR: 2016/01/01 00:00; 2014/11/24 [aheadofprint]; ppublish