Clinical trial · Interventional
S0221 Adjuvant Doxorubicin, Cyclophosphamide, and Paclitaxel in Treating Patients With Breast Cancer
Phase III Trial of Continuous Schedule AC + G vs. Q 2 Week Schedule AC, Followed by Paclitaxel Given Either Every 2 Weeks or Weekly for 12 Weeks as Post-Operative Adjuvant Therapy in Node-Positive or High-Risk Node-Negative Breast Cancer
NCT00070564CI-TRIAL-00124390active not recruitingPhase 3Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them after surgery may kill any remaining tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating resected breast cancer. PURPOSE: This randomized phase III trial is comparing 2 different regimens of combination chemotherapy to see how well they work in treating patients who have undergone surgery for stage I, stage II, or stage III breast cancer.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Breast Cancer | Malignant Breast Neoplasm | CURATED_EXACT | 0.92 |
Interventions
Interventions (5)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| AC regimen | Drug | — | UNRESOLVED |
| cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| doxorubicin hydrochloride | Drug | Doxorubicin | ALIAS |
| paclitaxel | Drug | Paclitaxel | ALIAS |
| pegfilgrastim | Biological | Pegfilgrastim | ALIAS |
Design
Arms and outcomes
Arms (6)
- type
- ACTIVE_COMPARATOR
- label
- Arm I
- description
- (closed 11/10/10) Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim subcutaneously (SC) on day 2 or filgrastim (G-CSF) SC on days 3-10. Treatment repeats every 14 days for 6 courses. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 3 hours on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses.
- interventionNames
- Biological: pegfilgrastim
- Drug: AC regimen
- Drug: cyclophosphamide
- Drug: doxorubicin hydrochloride
- Drug: paclitaxel
- type
- EXPERIMENTAL
- label
- Arm II
- description
- (closed 11/10/10) Patients receive doxorubicin IV on day 1, oral cyclophosphamide on days 1-7, and G-CSF SC on days 2-7. Treatment repeats every 7 days for 15 courses. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel and pegfilgrastim as in arm I.
- interventionNames
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
DISEASE CHARACTERISTICS:
* Histologically confirmed stage I-III invasive breast cancer
* Operable disease
* Stage I, II, IIIA, and IIIC (T1-3, N3a only)
* No T4 tumors
* High-risk disease, defined by 1 of the following:
* Tumor ≥ 2 cm in greatest diameter (includes both invasive and intraductal component)
* Patients with nodal status of N0+ (i.e., no cluster of tumor cells in any node greater than 0.2 mm) are considered to be node negative and must have a primary tumor ≥ 2 cm in size or have a tumor ≥ 1 cm with high risk features
* Patients who are node negative on the basis of a sentinel node procedure and fewer than 6 axillary nodes are removed are eligible OR at least 6 axillary or intramammary nodes must be negative
* Tumor ≥ 1 cm in diameter and meeting 1 of the following criteria:
* ER-negative and PgR-negative
* ER-positive or PgR-positive with a Genomic Health Recurrence Score of ≥ 26
* One or more axillary or intramammary nodes are involved by metastatic breast cancer
* If one or more nodes is involved, a minimum of 6 axillary or intramammary nodes must have been examined histologically
* Patients with N0(I+) disease will be considered node negative
* HER2/neu-positive tumors (3+ by immunohistochemical staining or amplified by fluorescence in-situ hybridization) allowed
* Bilateral synchronous breast cancer diagnosed within 1 month of each other allowed provided the higher TNM stage primary tumor meets the eligibility criteria
* Prior modified radical mastectomy OR local excision of all tumors with axillary lymph node dissection or sentinel node resection required
* No more than 84 days since prior surgery for the primary tumor and/or axilla
* Final resection margins for the primary tumor must be histologically negative for invasive cancer and ductal carcinoma in situ
* Resection margins positive for lobular carcinoma in situ are allowed
* Hormone receptor status:
* Estrogen receptor status known
* Progesterone receptor status known
PATIENT CHARACTERISTICS:
Age
* 18 and over
Sex
* Male or female
Menopausal status
* Not specified
Performance status
* Zubrod 0-2
Life expectancy
* Not specified
Hematopoietic
* Absolute neutrophil count at least 1,200/mm\^3
* Platelet count at least 100,000/mm\^3
Hepatic
* Bilirubin no greater than upper limit of normal (ULN)
* Alkaline phosphatase no greater than 2 times ULN
* SGOT or SGPT no greater than 2 times ULN
Renal
* Creatinine no greater than ULN
Cardiovascular
* No congestive heart failure
* No active angina pectoris
* LVEF greater than or equal to the lower limit of normal\* by MUGA or echocardiogram NOTE: Patients age 60 and over OR with a history of hypertension
Other
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, in situ cervical carcinoma, or lobular carcinoma in situ of the breast
* Prior invasive breast cancer or ductal carcinoma in situ allowed if disease-free for 5 years
* HIV negative
PRIOR CONCURRENT THERAPY:
Biologic therapy
* Not specified
Chemotherapy
* No prior cytotoxic chemotherapy for this breast cancer
* No prior chemotherapy with an anthracycline, anthracenedione, or taxane
Endocrine therapy
* Not specified
Radiotherapy
* No prior radiotherapy for this malignancy
* At least 2 weeks since prior radiotherapy for ductal carcinoma in situ
Surgery
* See Disease CharacteristicsReferences
Publications (4)
- RESULTBudd GT, Barlow WE, Moore HC, Hobday TJ, Stewart JA, Isaacs C, Salim M, Cho JK, Rinn KJ, Albain KS, Chew HK, Burton GV, Moore TD, Srkalovic G, McGregor BA, Flaherty LE, Livingston RB, Lew DL, Gralow JR, Hortobagyi GN. SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer. J Clin Oncol. 2015 Jan 1;33(1):58-64. doi: 10.1200/JCO.2014.56.3296. Epub 2014 Nov 24. PMID 25422488
- RESULTSucheston LE, Zhao H, Yao S, Zirpoli G, Liu S, Barlow WE, Moore HC, Thomas Budd G, Hershman DL, Davis W, Ciupak GL, Stewart JA, Isaacs C, Hobday TJ, Salim M, Hortobagyi GN, Gralow JR, Livingston RB, Albain KS, Hayes DF, Ambrosone CB. Genetic predictors of taxane-induced neurotoxicity in a SWOG phase III intergroup adjuvant breast cancer treatment trial (S0221). Breast Cancer Res Treat. 2011 Dec;130(3):993-1002. doi: 10.1007/s10549-011-1671-3. Epub 2011 Jul 16. PMID 21766209
- RESULTAmbrosone CB, Sucheston LE, Zhao H, et al.: Variants in the BRCA1/Fanconi-anemia repair pathway and taxane-induced neuropathy in SWOG S0221. [Abstract] 32nd Annual San Antonio Breast Cancer Symposium, December 9-13, 2009, San Antonio, Texas. A-2001, 2009.
- DERIVEDChen CS, Zirpoli G, Barlow WE, Budd GT, McKiver B, Pusztai L, Hortobagyi GN, Albain KS, Damaj MI, Godwin AK, Thompson A, Henry NL, Ambrosone CB, Stringer KA, Hertz DL. Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221. J Natl Compr Canc Netw. 2023 Nov;21(11):1172-1180.e3. doi: 10.6004/jnccn.2023.7062. PMID 37935109