S0221 Adjuvant Doxorubicin, Cyclophosphamide, and Paclitaxel in Treating Patients With Breast Cancer

Sponsor

Southwest Oncology Group (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00070564

Collaborator

National Cancer Institute (NCI) (NIH)

3,294

Enrollment

542

Locations

Arms

278

Duration (Months)

6.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: pegfilgrastim Drug: AC regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel	Phase 3

Detailed Description

OBJECTIVES:

Compare the disease-free survival of patients with node-positive or high-risk node-negative breast cancer treated with 2 different schedules of adjuvant doxorubicin, cyclophosphamide, and paclitaxel.
Compare the overall survival of patients treated with these regimens.
Compare the toxic effects of these regimens in these patients.
Correlate outcome with putative prognostic markers in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms (arms V and VI) (arms I-IV closed 11/10/10).

Arm I: (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.

Arm II: (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.

Arm III: (closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I.

Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.

Arm IV: (closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II.

Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III.

Arm V: Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses.

Arm VI: Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim as in arm V.

Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

In all arms patients with HER2/neu-positive tumors also receive trastuzumab (Herceptin®) weekly or every 3 weeks beginning concurrently with paclitaxel OR 3 months after the last dose of paclitaxel and continuing for up to 52 weeks.

In all arms, patients with estrogen-receptor or progesterone-receptor positive tumors receive hormonal therapy beginning within 28 days of the completion of adjuvant chemotherapy or radiotherapy (if given).

After finishing study treatment patients are followed up every 6 months for 5 years and then once a year for up to 15 years.

PROJECTED ACCRUAL: A total of 3,250 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

3294 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2003

Actual Primary Completion Date :

Jan 1, 2015

Anticipated Study Completion Date :

Jan 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (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.	Biological: pegfilgrastim Given IV Drug: AC regimen Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: paclitaxel Given IV
Experimental: Arm II (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.	Biological: pegfilgrastim Given IV Drug: AC regimen Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: paclitaxel Given IV
Active Comparator: Arm III (closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.	Biological: pegfilgrastim Given IV Drug: AC regimen Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: paclitaxel Given IV
Experimental: Arm IV (closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III.	Biological: pegfilgrastim Given IV Drug: AC regimen Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: paclitaxel Given IV
Experimental: Arm V Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. 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.	Biological: pegfilgrastim Given IV Drug: AC regimen Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: paclitaxel Given IV
Experimental: Arm VI Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim as in arm V. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.	Biological: pegfilgrastim Given IV Drug: AC regimen Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: paclitaxel Given IV

Outcome Measures

Primary Outcome Measures

Disease-free Survival [every 6 months (annually for mammograms) for 5 years]
Disease-free survival (DFS) defined as time from registration (randomization assignment) to first instance of disease recurrence (local, regional, or distant), new breast primary tumor, or death as a result of any cause. The results are entered as disease free survival at year 5.
Overall Survival [Every 6 months for 5 years]
Overall survival defined as time from registration to death as result of any cause. Results were entered as overall survival rate at year 5.

Secondary Outcome Measures

Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs [Toxicity assessment was evaluated every 4 weeks while on protocol therapy.]
Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Disease-free Survival Comparison Between 2 Treatments in HR-positive, HER-2 Negative Group [Biomarkers were measured by gene expression analysis before study entry. DFS were measured every 6 months for 5 years]
Disease-free survival (DFS) defined as time from registration (randomization assignment) to first instance of disease recurrence (local, regional, or distant), new breast primary tumor, or death as a result of any cause. The results are entered as disease free survival at year 5.
Overall Survival Comparison Between 2 Treatments in HR-positive, HER-2 Negative Group [Biomarkers were measured by gene expression analysis before study entry. OS was measured every 6 months for 5 years]
Overall survival defined as time from registration to death as result of any cause. Results were entered as overall survival rate at year 5.
Disease-free Survival Comparison Between 2 Treatments in HR-negative, HER-2 Negative Group [Biomarkers were measured by gene expression analysis before study entry. DFS was measured every 6 months for 5 years]
Disease-free survival (DFS) defined as time from registration (randomization assignment) to first instance of disease recurrence (local, regional, or distant), new breast primary tumor, or death as a result of any cause. The results are entered as disease free survival at year 5.
Overall Survival Comparison Between 2 Treatments in HR-negative, HER-2 Negative Group [Biomarkers were measured by gene expression analysis before study entry. OS was measured every 6 months for 5 years]
Overall survival defined as time from registration to death as result of any cause. Results were entered as overall survival rate at year 5.
Disease-free Survival Comparison Between 2 Treatments in HER2-positive Group [Biomarkers were measured by gene expression analysis before study entry. DFS was measured every 6 months for 5 years]
Disease-free survival (DFS) defined as time from registration (randomization assignment) to first instance of disease recurrence (local, regional, or distant), new breast primary tumor, or death as a result of any cause. The results are entered as disease free survival at year 5.
Overall Survival Comparison Between 2 Treatments in HER-2 Positive Group. [Biomarkers were measured by gene expression analysis before study entry. OS was measured every 6 months for 5 years]
Overall survival defined as time from registration to death as result of any cause. Results were entered as overall survival rate at year 5.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 Characteristics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Regional Medical Center	Anniston	Alabama	United States	36207
2	UAB Comprehensive Cancer Center	Birmingham	Alabama	United States	35294
3	Providence Cancer Center at Providence Hospital	Mobile	Alabama	United States	36608
4	Providence Cancer Center	Anchorage	Alaska	United States	99508
5	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
6	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724-5024
7	Hembree Mercy Cancer Center at St. Edward Mercy Medical Center	Fort Smith	Arkansas	United States	72903
8	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
9	Alta Bates Summit Comprehensive Cancer Center	Berkeley	California	United States	94704
10	Peninsula Medical Center	Burlingame	California	United States	94010
11	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
12	Valley Medical Oncology Consultants - Castro Valley	Castro Valley	California	United States	94546
13	Valley Medical Oncology	Fremont	California	United States	94538
14	California Cancer Center - Woodward Park Office	Fresno	California	United States	93720
15	Todd Cancer Institute at Long Beach Memorial Medical Center	Long Beach	California	United States	90806
16	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
17	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
18	Tibotec Therapeutics - Division of Ortho Biotech Products, LP	Marysville	California	United States	95901
19	Memorial Medical Center	Modesto	California	United States	95355
20	El Camino Hospital Cancer Center	Mountain View	California	United States	94040
21	Sutter Health - Western Division Cancer Research Group	Novato	California	United States	94945
22	Highland General Hospital	Oakland	California	United States	94602
23	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
24	Bay Area Breast Surgeons, Incorporated	Oakland	California	United States	94609
25	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609
26	Larry G Strieff MD Medical Corporation	Oakland	California	United States	94609
27	Tom K Lee, Incorporated	Oakland	California	United States	94609
28	St. Joseph Hospital Regional Cancer Center - Orange	Orange	California	United States	92868
29	Desert Regional Medical Center Comprehensive Cancer Center	Palm Springs	California	United States	92262
30	Valley Medical Oncology Consultants - Pleasanton	Pleasanton	California	United States	94588
31	Sutter Cancer Center at Roseville Medical Center	Roseville	California	United States	95661
32	Sutter Cancer Center	Sacramento	California	United States	95816
33	University of California Davis Cancer Center	Sacramento	California	United States	95817
34	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
35	California Pacific Medical Center - California Campus	San Francisco	California	United States	94118
36	Doctors Medical Center - San Pablo Campus	San Pablo	California	United States	94806
37	Sutter Solano Medical Center	Vallejo	California	United States	94589
38	San Luis Valley Regional Medical Center	Alamosa	Colorado	United States	81101
39	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado	United States	80045
40	Memorial Hospital Cancer Center - Colorado Springs	Colorado Springs	Colorado	United States	80909
41	Denver Health Medical Center	Denver	Colorado	United States	80204
42	Veterans Affairs Medical Center - Denver	Denver	Colorado	United States	80220
43	Shaw Regional Cancer Center	Edwards	Colorado	United States	81632
44	Valley View Hospital Cancer Center	Glenwood Springs	Colorado	United States	81601
45	Montrose Memorial Hospital Cancer Center	Montrose	Colorado	United States	81401
46	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
47	Yale Cancer Center	New Haven	Connecticut	United States	06520-8028
48	Washington Cancer Institute at Washington Hospital Center	Washington	District of Columbia	United States	20010
49	Herbert D. Kerman Regional Oncology Center - Daytona Beach	Daytona Beach	Florida	United States	32114
50	Florida Hospital Memorial Medical Center	Daytona Beach	Florida	United States	32117
51	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
52	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
53	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida	United States	33458
54	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
55	Piedmont Hospital	Atlanta	Georgia	United States	30309
56	Northside Hospital Cancer Center	Atlanta	Georgia	United States	30342-1611
57	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia	United States	30342-1701
58	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342
59	WellStar Cobb Hospital	Austell	Georgia	United States	30106
60	John B. Amos Cancer Center	Columbus	Georgia	United States	31904
61	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia	United States	30033
62	Piedmont Fayette Hospital	Fayetteville	Georgia	United States	30214
63	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia	United States	30905-5650
64	Gwinnett Medical Center	Lawrenceville	Georgia	United States	30045
65	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia	United States	30060
66	Southern Regional Medical Center	Riverdale	Georgia	United States	30274-2600
67	Harbin Clinic Cancer Center - Medical Oncology	Rome	Georgia	United States	30165
68	Pearlman Comprehensive Cancer Center at South Georgia Medical Center	Valdosta	Georgia	United States	31603
69	Kapiolani Medical Center at Pali Momi	'Aiea	Hawaii	United States	96701
70	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
71	OnCare Hawaii, Incorporated - Lusitana	Honolulu	Hawaii	United States	96813
72	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii	United States	96813
73	Straub Clinic and Hospital, Incorporated	Honolulu	Hawaii	United States	96813
74	Hawaii Medical Center - East	Honolulu	Hawaii	United States	96817
75	OnCare Hawaii, Incorporated - Kuakini	Honolulu	Hawaii	United States	96817
76	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
77	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859
78	Castle Medical Center	Kailua	Hawaii	United States	96734
79	Kauai Medical Clinic	Lihue	Hawaii	United States	96766
80	Maui Memorial Medical Center	Wailuku	Hawaii	United States	96793
81	Pacific Cancer Institute - Maui	Wailuku	Hawaii	United States	96793
82	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
83	Mountain States Tumor Institute at St. Luke's Regional Medical Center	Boise	Idaho	United States	83712
84	Kootenai Cancer Center - Coeur d'Alene	Coeur d'Alene	Idaho	United States	83814
85	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois	United States	62002
86	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
87	Illinois CancerCare - Bloomington	Bloomington	Illinois	United States	61701
88	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
89	Graham Hospital	Canton	Illinois	United States	61520
90	Illinois CancerCare - Canton	Canton	Illinois	United States	61520
91	Illinois CancerCare - Carthage	Carthage	Illinois	United States	62321
92	Memorial Hospital	Carthage	Illinois	United States	62321
93	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
94	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
95	Resurrection Medical Center	Chicago	Illinois	United States	60631
96	Saint Joseph Hospital	Chicago	Illinois	United States	60657
97	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
98	Sherman Hospital	Elgin	Illinois	United States	60123
99	Elmhurst Memorial Hospital	Elmhurst	Illinois	United States	60126
100	Eureka Community Hospital	Eureka	Illinois	United States	61530
101	Illinois CancerCare - Eureka	Eureka	Illinois	United States	61530
102	St. Francis Hospital	Evanston	Illinois	United States	60202
103	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
104	Illinois CancerCare - Galesburg	Galesburg	Illinois	United States	61401
105	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
106	Illinois CancerCare - Havana	Havana	Illinois	United States	62644
107	Mason District Hospital	Havana	Illinois	United States	62644
108	Kellogg Cancer Care Center	Highland Park	Illinois	United States	60035
109	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
110	Provena St. Mary's Regional Cancer Center - Kankakee	Kankakee	Illinois	United States	60901
111	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois	United States	61443
112	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois	United States	60048
113	Illinois CancerCare - Macomb	Macomb	Illinois	United States	61455
114	McDonough District Hospital	Macomb	Illinois	United States	61455
115	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
116	Illinois CancerCare - Monmouth	Monmouth	Illinois	United States	61462
117	OSF Holy Family Medical Center	Monmouth	Illinois	United States	61462
118	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
119	Edward Hospital Cancer Center	Naperville	Illinois	United States	60540
120	Hematology Oncology Consultants - Naperville	Naperville	Illinois	United States	60540
121	Cancer Care and Hematology Specialists of Chicagoland - Niles	Niles	Illinois	United States	60714
122	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
123	Community Cancer Center	Normal	Illinois	United States	61761
124	Illinois CancerCare - Community Cancer Center	Normal	Illinois	United States	61761
125	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
126	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
127	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
128	Illinois CancerCare - Pekin	Pekin	Illinois	United States	61603
129	Proctor Hospital	Peoria	Illinois	United States	61614
130	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
131	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
132	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
133	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
134	Illinois CancerCare - Peru	Peru	Illinois	United States	61354
135	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
136	Illinois CancerCare - Princeton	Princeton	Illinois	United States	61356
137	Perry Memorial Hospital	Princeton	Illinois	United States	61356
138	Swedish-American Regional Cancer Center	Rockford	Illinois	United States	61104-2315
139	Hematology Oncology Associates - Skokie	Skokie	Illinois	United States	60076
140	Illinois CancerCare - Spring Valley	Spring Valley	Illinois	United States	61362
141	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
142	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
143	Central Dupage Cancer Center	Warrenville	Illinois	United States	60555
144	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
145	Elkhart Clinic, LLC	Elkhart	Indiana	United States	46514-2098
146	Michiana Hematology-Oncology, PC - Elkhart	Elkhart	Indiana	United States	46514
147	Elkhart General Hospital	Elkhart	Indiana	United States	46515
148	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana	United States	46845
149	Howard Community Hospital	Kokomo	Indiana	United States	46904
150	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
151	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
152	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana	United States	46545-1470
153	Saint Joseph Regional Medical Center	Mishawaka	Indiana	United States	46545-1470
154	Michiana Hematology Oncology PC - Plymouth	Plymouth	Indiana	United States	46563
155	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
156	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
157	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
158	Michiana Hematology Oncology PC - La Porte	Westville	Indiana	United States	46391
159	McFarland Clinic, PC	Ames	Iowa	United States	50010
160	Hematology Oncology Associates of the Quad Cities	Bettendorf	Iowa	United States	52722
161	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
162	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
163	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
164	Heartland Oncology and Hematology	Council Bluffs	Iowa	United States	51503
165	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa	United States	52803
166	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
167	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
168	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
169	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
170	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
171	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
172	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
173	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
174	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
175	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51102
176	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
177	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
178	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
179	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
180	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
181	Hays Medical Center	Hays	Kansas	United States	67601
182	Hutchinson Hospital Corporation	Hutchinson	Kansas	United States	67502
183	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
184	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
185	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
186	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
187	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67901
188	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
189	Menorah Medical Center	Overland Park	Kansas	United States	66209
190	Saint Luke's Hospital - South	Overland Park	Kansas	United States	66213
191	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
192	Mount Carmel Regional Cancer Center	Pittsburg	Kansas	United States	66762
193	CCOP - Kansas City	Prairie Village	Kansas	United States	66208
194	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
195	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
196	Cotton-O'Neil Cancer Center	Topeka	Kansas	United States	66606
197	St. Francis Comprehensive Cancer Center	Topeka	Kansas	United States	66606
198	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
199	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
200	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
201	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
202	CCOP - Wichita	Wichita	Kansas	United States	67214
203	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
204	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
205	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana	United States	71315-3198
206	Ochsner Health Center - Bluebonnet	Baton Rouge	Louisiana	United States	70809
207	Ochsner Health Center - Covington	Covington	Louisiana	United States	70433
208	Louisiana State University Health Sciences Center - Monroe	Monroe	Louisiana	United States	71210
209	New Orleans Cancer Institute at Memorial Medical Center	New Orleans	Louisiana	United States	70115
210	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
211	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
212	Christus Schumpert Cancer Treatment Center	Shreveport	Louisiana	United States	71101
213	Feist-Weiller Cancer Center at Louisiana State University Health Sciences	Shreveport	Louisiana	United States	71130-3932
214	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland	United States	21215
215	St. Agnes Hospital Cancer Center	Baltimore	Maryland	United States	21229
216	Regional Cancer Center at Western Maryland Health System - Sacred Heart Campus	Cumberland	Maryland	United States	21502
217	Peninsula Regional Medical Center	Salisbury	Maryland	United States	21801
218	Caritas St. Elizabeth's Medical Center	Brighton	Massachusetts	United States	02135-2997
219	Addison Gilbert Hospital	Gloucester	Massachusetts	United States	01930
220	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
221	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
222	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
223	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0942
224	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan	United States	49017
225	Bay Regional Medical Center	Bay City	Michigan	United States	48708
226	Mecosta County Medical Center	Big Rapids	Michigan	United States	49307
227	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
228	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
229	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
230	Hurley Medical Center	Flint	Michigan	United States	48503
231	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
232	CCOP - Grand Rapids	Grand Rapids	Michigan	United States	49503
233	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan	United States	49503
234	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
235	Foote Memorial Hospital	Jackson	Michigan	United States	49201
236	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
237	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
238	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
239	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan	United States	48910
240	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
241	Lapeer Regional Hospital	Lapeer	Michigan	United States	48446
242	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
243	MidMichigan Medical Center - Midland	Midland	Michigan	United States	48670
244	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
245	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
246	Clemens Regional Medical Center	Mount Clemens	Michigan	United States	48043
247	Mercy General Health Partners	Muskegon	Michigan	United States	49443
248	Michiana Hematology Oncology PC - Niles	Niles	Michigan	United States	49120
249	Northern Michigan Hospital	Petoskey	Michigan	United States	49770
250	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
251	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
252	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
253	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
254	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
255	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan	United States	49085
256	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan	United States	48075
257	Munson Medical Center	Traverse City	Michigan	United States	49684
258	St. John Macomb Hospital	Warren	Michigan	United States	48093
259	Metro Health Hospital	Wyoming	Michigan	United States	49519
260		Alexandria	Minnesota	United States	56308
261	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
262	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
263	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
264	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
265	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
266	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
267	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
268	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
269	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
270	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
271	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
272	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
273	Coborn Cancer Center	Saint Cloud	Minnesota	United States	56303
274	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
275	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
276	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
277	United Hospital	Saint Paul	Minnesota	United States	55102
278	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
279	Lakeview Hospital	Stillwater	Minnesota	United States	55082
280	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
281	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
282	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
283	Keesler Air Force Base Medical Center	Keesler Air Force Base	Mississippi	United States	39534
284	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi	United States	39581
285	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
286	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
287	Goldschmidt Cancer Center	Jefferson City	Missouri	United States	65109
288	Freeman Cancer Institute at Freeman Health System	Joplin	Missouri	United States	64804
289	St. John's Regional Medical Center	Joplin	Missouri	United States	64804
290	Truman Medical Center - Hospital Hill	Kansas City	Missouri	United States	64108
291	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri	United States	64111
292	St. Joseph Medical Center	Kansas City	Missouri	United States	64114
293	North Kansas City Hospital	Kansas City	Missouri	United States	64116
294	Parvin Radiation Oncology	Kansas City	Missouri	United States	64116
295	Heartland Hematology Oncology Associates, Incorporated	Kansas City	Missouri	United States	64118
296	Research Medical Center	Kansas City	Missouri	United States	64132
297	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
298	Liberty Hospital	Liberty	Missouri	United States	64068
299	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
300	Saint Joseph Oncology, Incorporated	Saint Joseph	Missouri	United States	64507
301	Midwest Hematology Oncology Group, Incorporated	Saint Louis	Missouri	United States	63109
302	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
303	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
304	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
305	Comprehensive Cancer Care, PC	Saint Louis	Missouri	United States	63141
306	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri	United States	63141
307	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
308	St. John's Regional Health Center	Springfield	Missouri	United States	65804
309	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
310	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
311	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
312	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59102
313	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
314	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
315	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
316	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
317	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
318	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
319	Northern Montana Hospital	Havre	Montana	United States	59501
320	St. Peter's Hospital	Helena	Montana	United States	59601
321	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
322	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
323	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
324	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
325	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
326	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
327	Immanuel Medical Center	Omaha	Nebraska	United States	68122
328	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
329	Lakeside Hospital	Omaha	Nebraska	United States	68130
330	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
331	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
332	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
333	New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care	Concord	New Hampshire	United States	03301
334	New Hampshire Oncology - Hematology, PA - Hooksett	Hooksett	New Hampshire	United States	03106
335	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
336	Dizzy Gillespie Cancer Institute at Englewood Hospital and Medical Center	Englewood	New Jersey	United States	07631
337	CCOP - Northern New Jersey	Hackensack	New Jersey	United States	07601
338	St. Barnabas Medical Center Cancer Center	Livingston	New Jersey	United States	07039
339	UMDNJ University Hospital	Newark	New Jersey	United States	07103
340	Somerset Medical Center	Somerville	New Jersey	United States	08876
341	Overlook Hospital	Summit	New Jersey	United States	07902
342	Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare	Vineland	New Jersey	United States	08360
343	Hematology Oncology Associates, PC	Albuquerque	New Mexico	United States	87106
344	Presbyterian Cancer Treatment Center at Presbyterian Kaseman Hospital	Albuquerque	New Mexico	United States	87110
345	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
346	University of New Mexico Cancer Center - South	Las Cruces	New Mexico	United States	88011
347	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
348	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York	United States	13057
349	Beth Israel Medical Center - Petrie Division	New York	New York	United States	10003-3803
350	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021
351	St. Luke's - Roosevelt Hospital Center - St.Luke's Division	New York	New York	United States	10025
352	Union State Bank Cancer Center at Nyack Hospital	Nyack	New York	United States	10960-1998
353	Highland Hospital of Rochester	Rochester	New York	United States	14620
354	Lipson Cancer and Blood Center at Rochester General Hospital	Rochester	New York	United States	14621
355	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York	United States	14642
356	Hope A Women's Cancer Center	Asheville	North Carolina	United States	28816
357	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
358	Batte Cancer Center at Northeast Medical Center	Concord	North Carolina	United States	28025
359	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
360	Kinston Medical Specialists	Kinston	North Carolina	United States	28501
361	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
362	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
363	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
364	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
365	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
366	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio	United States	44307
367	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
368	Barberton Citizens Hospital	Barberton	Ohio	United States	44203
369	Cleveland Clinic Beachwood Family Health and Surgery Center	Beachwood	Ohio	United States	44122
370	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
371	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
372	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio	United States	44708
373	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
374	Good Samaritan Hospital Cancer Treatment Center	Cincinnati	Ohio	United States	45220
375	Bethesda North Hospital	Cincinnati	Ohio	United States	45242
376	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
377	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio	United States	44111
378	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
379	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
380	CCOP - Columbus	Columbus	Ohio	United States	43215
381	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
382	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
383	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
384	Grandview Hospital	Dayton	Ohio	United States	45405
385	Good Samaritan Hospital	Dayton	Ohio	United States	45406
386	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
387	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
388	CCOP - Dayton	Dayton	Ohio	United States	45420
389	Grady Memorial Hospital	Delaware	Ohio	United States	43015
390	Community Cancer Center	Elyria	Ohio	United States	44035
391	Hematology Oncology Center	Elyria	Ohio	United States	44035
392	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
393	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
394	Wayne Hospital	Greenville	Ohio	United States	45331
395	Cleveland Clinic Cancer Center	Independence	Ohio	United States	44131
396	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
397	Fairfield Medical Center	Lancaster	Ohio	United States	43130
398	St. Rita's Medical Center	Lima	Ohio	United States	45801
399	Lima Memorial Hospital	Lima	Ohio	United States	45804
400	MedCentral - Mansfield Hospital	Mansfield	Ohio	United States	44903
401	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
402	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537-1839
403	Hillcrest Cancer Center at Hillcrest Hospital	Mayfield Heights	Ohio	United States	44124
404	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
405	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
406	Fisher-Titus Medical Center	Norwalk	Ohio	United States	44857
407	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
408	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
409	Parma Community General Hospital	Parma	Ohio	United States	44129
410	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
411	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
412	Cleveland Clinic Foundation - Strongsville	Strongsville	Ohio	United States	44136
413	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
414	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
415	Toledo Hospital	Toledo	Ohio	United States	43606
416	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
417	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
418	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
419	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
420	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
421	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
422	Fulton County Health Center	Wauseon	Ohio	United States	43567
423	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
424	Cleveland Clinic - Wooster	Wooster	Ohio	United States	44691
425	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
426	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
427	Cleo Craig Cancer Research Clinic	Lawton	Oklahoma	United States	73505
428	Cancer Care Associates - Norman	Norman	Oklahoma	United States	73071
429	Cancer Care Associates - Mercy Campus	Oklahoma City	Oklahoma	United States	73120
430	Cancer Care Associates at Troy and Dollie Smith Cancer Center	Oklahoma City	Oklahoma	United States	73120
431	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
432	Bay Area Hospital	Coos Bay	Oregon	United States	97420
433	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
434	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
435	Willamette Falls Hospital	Oregon City	Oregon	United States	97045
436	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon	United States	97210
437	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
438	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
439	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
440	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon	United States	97239-3098
441	Butler Memorial Hospital	Butler	Pennsylvania	United States	16001
442	Dale and Frances Hughes Cancer Center at Pocono Medical Center	East Stroudsburg	Pennsylvania	United States	18301
443	PinnacleHealth Regional Cancer Center at Polyclinic Hospital	Harrisburg	Pennsylvania	United States	17110-2098
444	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
445	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
446	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
447	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
448	Pottstown Memorial Regional Cancer Center	Pottstown	Pennsylvania	United States	19464
449	Guthrie Cancer Center at Guthrie Clinic Sayre	Sayre	Pennsylvania	United States	18840
450	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania	United States	18501
451	Hematology and Oncology Associates of Northeastern Pennsylvania	Scranton	Pennsylvania	United States	18508
452	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
453	Associates in Hematology-Oncology, PC at Crozer Regional Cancer Center	Upland	Pennsylvania	United States	19013
454	Susquehanna Cancer Center at Divine Providence Hospital	Williamsport	Pennsylvania	United States	17701
455	South Carolina Oncology Associates, PA	Columbia	South Carolina	United States	29210
456	Cancer Centers of the Carolinas - Easley	Easley	South Carolina	United States	29640
457	McLeod Regional Medical Center	Florence	South Carolina	United States	29501
458	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina	United States	29605
459	Cancer Centers of the Carolinas - Grove Commons	Greenville	South Carolina	United States	29605
460	Greenville Hospital Cancer Center	Greenville	South Carolina	United States	29605
461	CCOP - Greenville	Greenville	South Carolina	United States	29615
462	Self Regional Cancer Center at Self Regional Medical Center	Greenwood	South Carolina	United States	29646
463	Cancer Centers of the Carolinas - Greer Medical Oncology	Greer	South Carolina	United States	29650
464	Cancer Centers of the Carolinas - Seneca	Seneca	South Carolina	United States	29672
465	Cancer Centers of the Carolinas - Spartanburg	Spartanburg	South Carolina	United States	29307
466	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
467	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
468	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
469	University of Tennessee Cancer Institute - Memphis	Memphis	Tennessee	United States	38104
470	MBCCOP - Meharry Medical College - Nashville	Nashville	Tennessee	United States	37208-3599
471	Texas Tech University Health Sciences Center School of Medicine - El Paso	El Paso	Texas	United States	79905
472	University of Texas Medical Branch	Galveston	Texas	United States	77555-0361
473	UMC Southwest Cancer and Research Center	Lubbock	Texas	United States	79415-3364
474	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas	United States	78209
475	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229-3900
476	University Hospital - San Antonio	San Antonio	Texas	United States	78229
477	American Fork Hospital	American Fork	Utah	United States	84003
478	Sandra L. Maxwell Cancer Center	Cedar City	Utah	United States	84720
479	Logan Regional Hospital	Logan	Utah	United States	84321
480	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah	United States	84157
481	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah	United States	84403
482	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
483	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
484	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah	United States	84106
485	LDS Hospital	Salt Lake City	Utah	United States	84143
486	Green Mountain Oncology Group	Bennington	Vermont	United States	05201
487	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
488	Hematology-Oncology Associates of Fredericksburg, Incorporated	Fredericksburg	Virginia	United States	22408
489	Island Hospital Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
490	St. Joseph Cancer Center	Bellingham	Washington	United States	98225
491	Olympic Hematology and Oncology	Bremerton	Washington	United States	98310
492	Highline Medical Center Cancer Center	Burien	Washington	United States	98166
493	Providence Centralia Hospital	Centralia	Washington	United States	98531-9027
494	St. Francis Hospital	Federal Way	Washington	United States	98003
495	Columbia Basin Hematology	Kennewick	Washington	United States	99336
496	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington	United States	98274
497	Providence St. Peter Hospital Regional Cancer Center	Olympia	Washington	United States	98506-5166
498	Harrison Poulsbo Hematology and Onocology	Poulsbo	Washington	United States	98370
499	Good Samaritan Cancer Center	Puyallup	Washington	United States	98372
500	Harborview Medical Center	Seattle	Washington	United States	98104
501	Minor and James Medical, PLLC	Seattle	Washington	United States	98104
502	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
503	Group Health Central Hospital	Seattle	Washington	United States	98112
504	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
505	University Cancer Center at University of Washington Medical Center	Seattle	Washington	United States	98195
506	North Puget Oncology at United General Hospital	Sedro-Woolley	Washington	United States	98284
507	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
508	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington	United States	99204
509	Evergreen Hematology and Oncology, PS	Spokane	Washington	United States	99218
510	Franciscan Cancer Center at St. Joseph Medical Center	Tacoma	Washington	United States	98405-3004
511	Allenmore Hospital	Tacoma	Washington	United States	98405
512	CCOP - Northwest	Tacoma	Washington	United States	98405
513	MultiCare Regional Cancer Center at Tacoma General Hospital	Tacoma	Washington	United States	98405
514	Madigan Army Medical Center - Tacoma	Tacoma	Washington	United States	98431
515	St. Clare Hospital	Tacoma	Washington	United States	98499
516	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98664
517	Northwest Cancer Specialists at Vancouver Cancer Center	Vancouver	Washington	United States	98684
518	Wenatchee Valley Medical Center	Wenatchee	Washington	United States	98801-2028
519	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
520	Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital	Parkersburg	West Virginia	United States	26102
521	Princeton Community Hospital	Princeton	West Virginia	United States	24740
522	Langlade Memorial Hospital	Antigo	Wisconsin	United States	54409
523	Fox Valley Hematology and Oncology - East Grant Street	Appleton	Wisconsin	United States	54911-3496
524	Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
525	UW Cancer Center Johnson Creek	Johnson Creek	Wisconsin	United States	53038
526	Franciscan Skemp Healthcare - La Crosse Campus	La Crosse	Wisconsin	United States	54601
527	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin	United States	54601
528	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
529	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin	United States	54221-1450
530	Vince Lombardi Cancer Clinic - Marinette	Marinette	Wisconsin	United States	54143
531	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
532	All Saints Cancer Center at Wheaton Franciscan Healthcare	Racine	Wisconsin	United States	53405
533	Vince Lombardi Cancer Clinic - Sheboygan	Sheboygan	Wisconsin	United States	53081
534	Aurora Medical Center	Summit	Wisconsin	United States	53066
535	Vince Lombardi Cancer Clinic - Two Rivers	Two Rivers	Wisconsin	United States	54241
536	University of Wisconcin Cancer Center at Aspirus Wausau Hospital	Wausau	Wisconsin	United States	54401
537	Oncology Alliance, SC - Milwaukee - West	Wauwatosa	Wisconsin	United States	53226
538	Riverview UW Cancer Center at Riverview Hospital	Wisconsin Rapids	Wisconsin	United States	54494
539	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801
540	Cancer Care Program at Thunder Bay Regional Health Sciences	Thunder Bay	Ontario	Canada	P7B 6V4
541	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan	Canada	S4T 7T1
542	San Juan City Hospital	San Juan		Puerto Rico	00936

Sponsors and Collaborators

Southwest Oncology Group
National Cancer Institute (NCI)

Investigators

Study Chair: George Thomas Budd, MD, The Cleveland Clinic
Study Director: Halle C Moore, MD, The Cleveland Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Southwest Oncology Group

ClinicalTrials.gov Identifier:

NCT00070564

Other Study ID Numbers:

CDR0000334899
S0221
U10CA032102

First Posted:

Oct 7, 2003

Last Update Posted:

Jan 21, 2022

Last Verified:

Jan 1, 2022

Keywords provided by Southwest Oncology Group

stage II breast cancer

stage IA breast cancer

stage IB breast cancer

stage IIIC breast cancer

male breast cancer

HER2-positive breast cancer

estrogen receptor-negative breast cancer

estrogen receptor-positive breast cancer

progesterone receptor-negative breast cancer

progesterone receptor-positive breast cancer

Additional relevant MeSH terms:

Liposomal doxorubicin

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	Arm I	Arm II	Arm III	Arm IV	Arm V	Arm VI
Arm/Group 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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(reopened in 12/2010) Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. 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.	(reopened in 12/2010) Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.
Period Title: Overall Study
STARTED	678	693	697	648	282	296
COMPLETED	478	490	526	481	203	244
NOT COMPLETED	200	203	171	167	79	52

Baseline Characteristics

Arm/Group Title	Arm I	Arm II	Arm III	Arm IV	Arm V	ARM VI	Total
Arm/Group 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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(reopened in 12/2010) Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. 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.	(reopened in 12/2010) Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.	Total of all reporting groups
Overall Participants	664	683	681	639	277	294	3238
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	50.5	50.9	51.8	50.7	52.7	53.2	52.7
Sex: Female, Male (Count of Participants)
Female	658 99.1%	679 99.4%	676 99.3%	636 99.5%	275 99.3%	291 99%	3215 99.3%
Male	6 0.9%	4 0.6%	5 0.7%	3 0.5%	2 0.7%	3 1%	23 0.7%
Black Race (Count of Participants)
Count of Participants [Participants]	73 11%	77 11.3%	74 10.9%	78 12.2%	31 11.2%	44 15%	377 11.6%
Menopausal status (females) (Count of Participants)
Premenopausal	326 49.1%	325 47.6%	308 45.2%	299 46.8%	124 44.8%	123 41.8%	1505 46.5%
Postmenopausal	332 50%	354 51.8%	368 54%	337 52.7%	148 53.4%	166 56.5%	1705 52.7%
Unknown	0 0%	0 0%	0 0%	0 0%	3 1.1%	2 0.7%	5 0.2%
Nodal status (Count of Participants)
Negative	161 24.2%	153 22.4%	159 23.3%	146 22.8%	105 37.9%	109 37.1%	833 25.7%
1-3 positive nodes	260 39.2%	266 38.9%	276 40.5%	245 38.3%	103 37.2%	98 33.3%	1248 38.5%
>= 4 positive nodes	241 36.3%	264 38.7%	243 35.7%	244 38.2%	68 24.5%	87 29.6%	1147 35.4%
unknown	2 0.3%	0 0%	3 0.4%	4 0.6%	1 0.4%	0 0%	10 0.3%
ER/PgR (Count of Participants)
Negative (both negative)	212 31.9%	226 33.1%	232 34.1%	206 32.2%	99 35.7%	108 36.7%	1083 33.4%
Positive (either or both positive)	450 67.8%	456 66.8%	446 65.5%	430 67.3%	178 64.3%	185 62.9%	2145 66.2%
Unknown	2 0.3%	1 0.1%	3 0.4%	3 0.5%	0 0%	1 0.3%	10 0.3%
HER2 (Count of Participants)
Negative	528 79.5%	556 81.4%	554 81.4%	525 82.2%	208 75.1%	235 79.9%	2606 80.5%
Positive	125 18.8%	123 18%	118 17.3%	109 17.1%	69 24.9%	57 19.4%	601 18.6%
Unknown	11 1.7%	4 0.6%	9 1.3%	5 0.8%	0 0%	2 0.7%	31 1%

Outcome Measures

1. Primary Outcome

Title	Disease-free Survival
Description	Disease-free survival (DFS) defined as time from registration (randomization assignment) to first instance of disease recurrence (local, regional, or distant), new breast primary tumor, or death as a result of any cause. The results are entered as disease free survival at year 5.
Time Frame	every 6 months (annually for mammograms) for 5 years

Outcome Measure Data

Analysis Population Description
Only eligible and analyzable patients were included in this analysis. Two patients in Arm II and one patient in Arm IV with no follow-up were excluded.

Arm/Group Title	Arm I	Arm II	Arm III	Arm IV	Arm V	Arm VI
Arm/Group 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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(reopened in 12/2010) Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. 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.	(reopened in 12/2010) Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.
Measure Participants	664	681	681	638	277	294
Number (95% Confidence Interval) [percentage of participants]	83 12.5%	79 11.6%	81 11.9%	81 12.7%	84 30.3%	85 28.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.022
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95% 1.04 to 1.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm III
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.072
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 95% 0.98 to 1.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm IV
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95% 0.87 to 1.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm V, Arm VI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.733
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95% 0.61 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Overall Survival
Description	Overall survival defined as time from registration to death as result of any cause. Results were entered as overall survival rate at year 5.
Time Frame	Every 6 months for 5 years

Outcome Measure Data

Analysis Population Description
Only eligible and analyzable patients were included in this analysis. Two patients in Arm II and one patient in Arm IV with no follow-up were excluded.

Arm/Group Title	Arm I	Arm II	Arm III	Arm IV	Arm V	Arm VI
Arm/Group 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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(reopened in 12/2010) Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. 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.	(reopened in 12/2010) Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.
Measure Participants	664	681	681	638	277	294
Number (95% Confidence Interval) [percentage of participants]	90 13.6%	87 12.7%	87 12.8%	87 13.6%	90 32.5%	91 31%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.44
	Confidence Interval	(2-Sided) 95% 1.08 to 1.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm III
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.46
	Confidence Interval	(2-Sided) 95% 1.09 to 1.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm IV
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 95% 0.91 to 1.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.040
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm V, Arm VI
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.724
	Comments
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95% 0.54 to 1.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Description	Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time Frame	Toxicity assessment was evaluated every 4 weeks while on protocol therapy.

Outcome Measure Data

Analysis Population Description
Limited to patients who started treatment, who did not have a major deviation in the treatment protocol, and whose toxicity profile has been completed.

Arm/Group Title	ARM I	ARM II	ARM III	ARM IV	ARM V	ARM VI
Arm/Group 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.	(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.	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III.	Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. 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.	(reopened in 12/2010) Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.
Measure Participants	654	663	674	624	275	291
ALT, SGPT (serum glutamic pyruvic transaminase)	7 1.1%	4 0.6%	3 0.4%	4 0.6%	3 1.1%	1 0.3%
AST, SGOT	5 0.8%	3 0.4%	2 0.3%	2 0.3%	4 1.4%	1 0.3%
Acidosis (metabolic or respiratory)	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Adult respiratory distress syndrome (ARDS)	1 0.2%	0 0%	2 0.3%	0 0%	0 0%	1 0.3%
Albumin, serum-low (hypoalbuminemia)	1 0.2%	2 0.3%	0 0%	0 0%	0 0%	0 0%
Alkaline phosphatase	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Allergic reaction/hypersensitivity	8 1.2%	12 1.8%	6 0.9%	3 0.5%	5 1.8%	5 1.7%
Anorexia	6 0.9%	5 0.7%	8 1.2%	4 0.6%	0 0%	2 0.7%
Apnea	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Arthritis (non-septic)	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.3%
Ataxia (incoordination)	2 0.3%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Bilirubin (hyperbilirubinemia)	3 0.5%	0 0%	2 0.3%	0 0%	0 0%	0 0%
Bladder spasms	0 0%	2 0.3%	0 0%	0 0%	0 0%	0 0%
Blood/Bone Marrow-Other	1 0.2%	2 0.3%	2 0.3%	0 0%	0 0%	0 0%
Bronchospasm, wheezing	0 0%	1 0.1%	0 0%	0 0%	1 0.4%	0 0%
CNS cerebrovascular ischemia	0 0%	0 0%	1 0.1%	1 0.2%	0 0%	0 0%
Calcium, serum-high (hypercalcemia)	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Calcium, serum-low (hypocalcemia)	2 0.3%	1 0.1%	1 0.1%	0 0%	1 0.4%	1 0.3%
Cardiac General-Other	2 0.3%	1 0.1%	1 0.1%	0 0%	0 0%	0 0%
Cardiac troponin I (cTnI)	0 0%	0 0%	1 0.1%	1 0.2%	0 0%	0 0%
Cardiac troponin T (cTnT)	3 0.5%	0 0%	2 0.3%	0 0%	0 0%	0 0%
Cardiac-ischemia/infarction	3 0.5%	0 0%	1 0.1%	0 0%	1 0.4%	0 0%
Cardiopulmonary arrest, cause unknown (non-fatal)	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Cataract	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Cholecystitis	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Colitis	1 0.2%	0 0%	2 0.3%	1 0.2%	1 0.4%	0 0%
Colitis, infectious (e.g., Clostridium difficile)	0 0%	0 0%	1 0.1%	2 0.3%	0 0%	0 0%
Conduction abnormality - Asystole	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Confusion	1 0.2%	1 0.1%	0 0%	0 0%	0 0%	1 0.3%
Constipation	3 0.5%	3 0.4%	3 0.4%	3 0.5%	1 0.4%	0 0%
Constitutional Symptoms-Other	1 0.2%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Cough	3 0.5%	5 0.7%	4 0.6%	0 0%	1 0.4%	1 0.3%
Creatinine	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Cystitis	0 0%	3 0.4%	0 0%	0 0%	0 0%	0 0%
Cytokine release syndrome/acute infusion reaction	0 0%	0 0%	0 0%	2 0.3%	1 0.4%	0 0%
DIC (disseminated intravascular coagulation)	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Death - Multi-organ failure	1 0.2%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Death not associated with CTCAE term - Death NOS	0 0%	0 0%	0 0%	1 0.2%	0 0%	1 0.3%
Dehydration	8 1.2%	7 1%	12 1.8%	3 0.5%	4 1.4%	4 1.4%
Dermatology/Skin-Other	0 0%	3 0.4%	0 0%	1 0.2%	1 0.4%	0 0%
Diarrhea	27 4.1%	18 2.6%	24 3.5%	23 3.6%	8 2.9%	6 2%
Distention/bloating, abdominal	0 0%	0 0%	1 0.1%	1 0.2%	0 0%	0 0%
Dizziness	5 0.8%	2 0.3%	2 0.3%	5 0.8%	0 0%	2 0.7%
Dysphagia (difficulty swallowing)	2 0.3%	0 0%	1 0.1%	3 0.5%	0 0%	0 0%
Dyspnea (shortness of breath)	21 3.2%	18 2.6%	25 3.7%	16 2.5%	2 0.7%	4 1.4%
Edema: head and neck	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Edema: limb	0 0%	2 0.3%	2 0.3%	3 0.5%	1 0.4%	1 0.3%
Encephalopathy	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Endocrine-Other	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Esophagitis	5 0.8%	4 0.6%	0 0%	3 0.5%	0 0%	0 0%
Extrapyramidal/involuntary movement/restlessness	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Extremity-upper (function)	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Eyelid dysfunction	0 0%	0 0%	0 0%	0 0%	1 0.4%	0 0%
FEV(1)	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Fatigue (asthenia, lethargy, malaise)	77 11.6%	59 8.6%	87 12.8%	65 10.2%	20 7.2%	14 4.8%
Febrile neutropenia	49 7.4%	9 1.3%	38 5.6%	20 3.1%	16 5.8%	14 4.8%
Fever in absence of neutropenia, ANC lt1.0x10e9/L	2 0.3%	3 0.4%	3 0.4%	1 0.2%	1 0.4%	1 0.3%
Fistula, GI - Oral cavity	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Flu-like syndrome	0 0%	1 0.1%	1 0.1%	1 0.2%	0 0%	0 0%
Fracture	0 0%	2 0.3%	0 0%	0 0%	0 0%	2 0.7%
GGT (gamma-glutamyl transpeptidase)	2 0.3%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Gastritis (including bile reflux gastritis)	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Gastrointestinal-Other	1 0.2%	0 0%	0 0%	3 0.5%	0 0%	0 0%
Glucose, serum-high (hyperglycemia)	13 2%	17 2.5%	9 1.3%	13 2%	6 2.2%	5 1.7%
Glucose, serum-low (hypoglycemia)	4 0.6%	2 0.3%	0 0%	1 0.2%	0 0%	0 0%
Hair loss/Alopecia (scalp or body)	3 0.5%	0 0%	0 0%	0 0%	0 0%	0 0%
Heartburn/dyspepsia	1 0.2%	0 0%	3 0.4%	5 0.8%	1 0.4%	1 0.3%
Hemoglobin	87 13.1%	48 7%	101 14.8%	47 7.4%	21 7.6%	19 6.5%
Hemorrhage, GI - Lower GI NOS	0 0%	1 0.1%	0 0%	1 0.2%	1 0.4%	0 0%
Hemorrhage, GI - Oral cavity	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Hemorrhage, GI - Rectum	1 0.2%	0 0%	0 0%	0 0%	1 0.4%	0 0%
Hemorrhage, GI - Upper GI NOS	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Hemorrhage, GU - Urinary NOS	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Hemorrhage, GU - Vagina	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Hemorrhage, pulmonary/upper respiratory - Nose	0 0%	0 0%	0 0%	1 0.2%	0 0%	1 0.3%
Hemorrhage/Bleeding-Other	1 0.2%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Hemorrhoids	1 0.2%	3 0.4%	1 0.1%	0 0%	0 0%	1 0.3%
Hot flashes/flushes	0 0%	2 0.3%	1 0.1%	0 0%	1 0.4%	1 0.3%
Hypertension	2 0.3%	1 0.1%	1 0.1%	1 0.2%	2 0.7%	2 0.7%
Hypotension	4 0.6%	1 0.1%	4 0.6%	3 0.5%	0 0%	3 1%
Hypoxia	2 0.3%	3 0.4%	3 0.4%	2 0.3%	3 1.1%	1 0.3%
INR (of prothrombin time)	2 0.3%	5 0.7%	1 0.1%	3 0.5%	1 0.4%	2 0.7%
Ileus, GI (functional obstruction of bowel)	0 0%	0 0%	1 0.1%	1 0.2%	0 0%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Abdomen NOS	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Bladder	0 0%	1 0.1%	1 0.1%	0 0%	0 0%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Blood	2 0.3%	1 0.1%	2 0.3%	0 0%	2 0.7%	3 1%
Inf (clin/microbio) w/Gr 3-4 neuts - Catheter-rel	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Colon	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.3%
Inf (clin/microbio) w/Gr 3-4 neuts - Eye NOS	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Lung	4 0.6%	2 0.3%	2 0.3%	4 0.6%	1 0.4%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Lymphatic	0 0%	0 0%	2 0.3%	0 0%	0 0%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Meninges	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.3%
Inf (clin/microbio) w/Gr 3-4 neuts - Middle ear	0 0%	0 0%	1 0.1%	1 0.2%	0 0%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Mucosa	1 0.2%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Oral cav-gums	0 0%	0 0%	1 0.1%	0 0%	0 0%	1 0.3%
Inf (clin/microbio) w/Gr 3-4 neuts - Paranasal	0 0%	0 0%	0 0%	2 0.3%	0 0%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Pharynx	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Skin	3 0.5%	1 0.1%	2 0.3%	3 0.5%	1 0.4%	2 0.7%
Inf (clin/microbio) w/Gr 3-4 neuts - Soft tissue	0 0%	0 0%	0 0%	0 0%	1 0.4%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - UTI	1 0.2%	2 0.3%	0 0%	1 0.2%	0 0%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Inf (clin/microbio) w/Gr 3-4 neuts - Wound	0 0%	2 0.3%	3 0.4%	0 0%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Bil. tree	0 0%	0 0%	0 0%	0 0%	1 0.4%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Bladder	0 0%	1 0.1%	1 0.1%	1 0.2%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Blood	2 0.3%	0 0%	0 0%	2 0.3%	0 0%	1 0.3%
Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus	0 0%	2 0.3%	0 0%	2 0.3%	1 0.4%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Catheter	0 0%	2 0.3%	2 0.3%	0 0%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Colon	0 0%	0 0%	1 0.1%	1 0.2%	0 0%	1 0.3%
Inf w/normal ANC or Gr 1-2 neutrophils - Dental	0 0%	1 0.1%	0 0%	1 0.2%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Esophagus	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Kidney	1 0.2%	1 0.1%	0 0%	0 0%	1 0.4%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	7 1.1%	5 0.7%	10 1.5%	5 0.8%	2 0.7%	4 1.4%
Inf w/normal ANC or Gr 1-2 neutrophils - Meninges	2 0.3%	0 0%	0 0%	0 0%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Muscle	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Neck NOS	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Oral cav	1 0.2%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Sinus	2 0.3%	2 0.3%	2 0.3%	0 0%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Skin	7 1.1%	6 0.9%	8 1.2%	11 1.7%	4 1.4%	4 1.4%
Inf w/normal ANC or Gr 1-2 neutrophils - Soft tiss	1 0.2%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - UTI	5 0.8%	3 0.4%	0 0%	1 0.2%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Ungual	0 0%	1 0.1%	1 0.1%	2 0.3%	0 0%	1 0.3%
Inf w/normal ANC or Gr 1-2 neutrophils - Up airway	0 0%	1 0.1%	2 0.3%	2 0.3%	1 0.4%	1 0.3%
Inf w/normal ANC or Gr 1-2 neutrophils - Vagina	0 0%	1 0.1%	0 0%	1 0.2%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Vulva	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils - Wound	0 0%	1 0.1%	0 0%	2 0.3%	1 0.4%	3 1%
Inf w/normal ANC or Gr 1-2 neutrophils - perioral	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils -Nerve-cran	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Inf w/normal ANC or Gr 1-2 neutrophils-Foreign bod	0 0%	1 0.1%	0 0%	0 0%	0 0%	1 0.3%
Infection with normal ANC or Grade 1 or 2 neutroph	1 0.2%	0 0%	1 0.1%	1 0.2%	0 0%	0 0%
Infection with unknown ANC - Appendix	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Infection with unknown ANC - Blood	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.3%
Infection with unknown ANC - Catheter-related	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Infection with unknown ANC - Foreign body (e.g., g	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.3%
Infection with unknown ANC - Kidney	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Infection with unknown ANC - Lung (pneumonia)	0 0%	1 0.1%	0 0%	0 0%	1 0.4%	0 0%
Infection with unknown ANC - Skin (cellulitis)	1 0.2%	0 0%	0 0%	0 0%	0 0%	1 0.3%
Infection with unknown ANC - Wound	0 0%	0 0%	0 0%	0 0%	1 0.4%	0 0%
Infection-Other	4 0.6%	3 0.4%	5 0.7%	0 0%	2 0.7%	1 0.3%
Injection site reaction/extravasation changes	1 0.2%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Insomnia	1 0.2%	1 0.1%	0 0%	6 0.9%	1 0.4%	1 0.3%
Intra-operative injury - Peripheral sensory NOS	0 0%	0 0%	0 0%	0 0%	0 0%	2 0.7%
Intra-operative injury - Spinal cord	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Irregular menses (change from baseline)	1 0.2%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Joint-function	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Left ventricular diastolic dysfunction	3 0.5%	0 0%	3 0.4%	0 0%	0 0%	0 0%
Left ventricular systolic dysfunction	7 1.1%	2 0.3%	8 1.2%	2 0.3%	1 0.4%	1 0.3%
Leukocytes (total WBC)	128 19.3%	98 14.3%	157 23.1%	128 20%	38 13.7%	34 11.6%
Liver dysfunction/failure (clinical)	1 0.2%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Lymphopenia	24 3.6%	31 4.5%	26 3.8%	32 5%	15 5.4%	18 6.1%
Magnesium, serum-low (hypomagnesemia)	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Metabolic/Laboratory-Other	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Mood alteration - agitation	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Mood alteration - anxiety	1 0.2%	2 0.3%	1 0.1%	0 0%	0 0%	0 0%
Mood alteration - depression	1 0.2%	6 0.9%	4 0.6%	4 0.6%	1 0.4%	2 0.7%
Mucositis/stomatitis (clinical exam) - Anus	0 0%	1 0.1%	0 0%	1 0.2%	0 0%	0 0%
Mucositis/stomatitis (clinical exam) - Esophagus	1 0.2%	0 0%	0 0%	2 0.3%	0 0%	0 0%
Mucositis/stomatitis (clinical exam) - Oral cavity	17 2.6%	56 8.2%	23 3.4%	57 8.9%	4 1.4%	3 1%
Mucositis/stomatitis (clinical exam) - Pharynx	2 0.3%	5 0.7%	3 0.4%	1 0.2%	0 0%	0 0%
Mucositis/stomatitis (functional/symp) - Anus	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Mucositis/stomatitis (functional/symp) - Esophagus	2 0.3%	3 0.4%	2 0.3%	5 0.8%	1 0.4%	1 0.3%
Mucositis/stomatitis (functional/symp) - Oral cav	11 1.7%	38 5.6%	28 4.1%	40 6.3%	1 0.4%	6 2%
Mucositis/stomatitis (functional/symp) - Pharynx	4 0.6%	4 0.6%	5 0.7%	4 0.6%	0 0%	1 0.3%
Mucositis/stomatitis (functional/symp) - Rectum	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Muscle weakness, not d/t neuropathy - Extrem-lower	0 0%	0 0%	0 0%	0 0%	2 0.7%	1 0.3%
Muscle weakness, not d/t neuropathy - body/general	0 0%	1 0.1%	1 0.1%	2 0.3%	1 0.4%	1 0.3%
Musculoskeletal/Soft Tissue-Other	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Myelodysplasia	0 0%	1 0.1%	1 0.1%	0 0%	0 0%	0 0%
Myocarditis	0 0%	0 0%	1 0.1%	0 0%	0 0%	1 0.3%
Nail changes	4 0.6%	12 1.8%	5 0.7%	9 1.4%	1 0.4%	1 0.3%
Nasal cavity/paranasal sinus reactions	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Nausea	50 7.5%	40 5.9%	53 7.8%	33 5.2%	9 3.2%	9 3.1%
Neurology-Other	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Neuropathy: CN V Motor-jaw muscles; Sensory-facial	1 0.2%	0 0%	1 0.1%	1 0.2%	0 0%	0 0%
Neuropathy: CN VII Motor-face; Sensory-taste	1 0.2%	0 0%	0 0%	0 0%	0 0%	1 0.3%
Neuropathy: cranial - CN VIII Hearing and balance	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Neuropathy: cranial - CN XII Motor-tongue	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Neuropathy: motor	10 1.5%	13 1.9%	8 1.2%	6 0.9%	5 1.8%	8 2.7%
Neuropathy: sensory	107 16.1%	101 14.8%	76 11.2%	56 8.8%	45 16.2%	25 8.5%
Neutrophils/granulocytes (ANC/AGC)	174 26.2%	156 22.8%	218 32%	201 31.5%	57 20.6%	65 22.1%
Obesity	0 0%	0 0%	0 0%	0 0%	1 0.4%	3 1%
Obstruction, GI - Small bowel NOS	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Opportunistic inf associated w/gt=Gr 2 lymphopenia	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
PTT (Partial thromboplastin time)	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Pain - Abdomen NOS	2 0.3%	3 0.4%	5 0.7%	0 0%	5 1.8%	2 0.7%
Pain - Anus	1 0.2%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Pain - Back	0 0%	5 0.7%	1 0.1%	3 0.5%	2 0.7%	2 0.7%
Pain - Bone	10 1.5%	36 5.3%	15 2.2%	9 1.4%	15 5.4%	1 0.3%
Pain - Breast	0 0%	0 0%	0 0%	0 0%	0 0%	2 0.7%
Pain - Cardiac/heart	1 0.2%	0 0%	0 0%	1 0.2%	1 0.4%	0 0%
Pain - Chest wall	1 0.2%	0 0%	0 0%	0 0%	1 0.4%	0 0%
Pain - Chest/thorax NOS	0 0%	1 0.1%	0 0%	3 0.5%	0 0%	0 0%
Pain - Dental/teeth/peridontal	0 0%	1 0.1%	0 0%	0 0%	0 0%	1 0.3%
Pain - Esophagus	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Pain - Extremity-limb	4 0.6%	9 1.3%	0 0%	3 0.5%	4 1.4%	1 0.3%
Pain - Head/headache	5 0.8%	8 1.2%	10 1.5%	10 1.6%	1 0.4%	0 0%
Pain - Joint	39 5.9%	40 5.9%	21 3.1%	12 1.9%	11 4%	5 1.7%
Pain - Kidney	0 0%	0 0%	0 0%	2 0.3%	0 0%	0 0%
Pain - Middle ear	0 0%	1 0.1%	0 0%	1 0.2%	0 0%	0 0%
Pain - Muscle	42 6.3%	48 7%	21 3.1%	11 1.7%	10 3.6%	5 1.7%
Pain - Neck	0 0%	1 0.1%	0 0%	0 0%	0 0%	1 0.3%
Pain - Neuralgia/peripheral nerve	1 0.2%	3 0.4%	2 0.3%	3 0.5%	1 0.4%	0 0%
Pain - Pain NOS	3 0.5%	0 0%	0 0%	1 0.2%	0 0%	1 0.3%
Pain - Pelvis	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Pain - Rectum	2 0.3%	1 0.1%	0 0%	2 0.3%	0 0%	0 0%
Pain - Skin	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Pain - Stomach	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Pain - Uterus	0 0%	0 0%	0 0%	0 0%	1 0.4%	0 0%
Pain-Other	3 0.5%	5 0.7%	2 0.3%	1 0.2%	4 1.4%	0 0%
Pericardial effusion (non-malignant)	0 0%	0 0%	0 0%	0 0%	0 0%	2 0.7%
Phosphate, serum-low (hypophosphatemia)	0 0%	3 0.4%	0 0%	2 0.3%	0 0%	0 0%
Platelets	24 3.6%	21 3.1%	20 2.9%	22 3.4%	6 2.2%	2 0.7%
Pleural effusion (non-malignant)	0 0%	1 0.1%	1 0.1%	0 0%	0 0%	1 0.3%
Pneumonitis/pulmonary infiltrates	8 1.2%	7 1%	11 1.6%	5 0.8%	3 1.1%	1 0.3%
Potassium, serum-high (hyperkalemia)	1 0.2%	1 0.1%	0 0%	1 0.2%	0 0%	0 0%
Potassium, serum-low (hypokalemia)	18 2.7%	12 1.8%	18 2.6%	7 1.1%	8 2.9%	8 2.7%
Prolapse of stoma, GI	2 0.3%	3 0.4%	2 0.3%	4 0.6%	0 0%	0 0%
Proteinuria	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Pruritus/itching	2 0.3%	3 0.4%	0 0%	1 0.2%	2 0.7%	1 0.3%
Psychosis (hallucinations/delusions)	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Pulmonary/Upper Respiratory-Other	1 0.2%	2 0.3%	1 0.1%	0 0%	1 0.4%	1 0.3%
Rash/desquamation	4 0.6%	5 0.7%	1 0.1%	4 0.6%	1 0.4%	1 0.3%
Rash: acne/acneiform	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Rash: hand-foot skin reaction	19 2.9%	95 13.9%	16 2.3%	94 14.7%	3 1.1%	4 1.4%
Restrictive cardiomyopathy	0 0%	0 0%	1 0.1%	1 0.2%	0 0%	0 0%
Right ventricular dysfunction (cor pulmonale)	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Rigors/chills	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
SVT and nodal arrhythmia - Atrial fibrillation	1 0.2%	1 0.1%	5 0.7%	1 0.2%	0 0%	0 0%
SVT and nodal arrhythmia - SVT tachycardia	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
SVT and nodal arrhythmia - Sinus tachycardia	0 0%	1 0.1%	1 0.1%	0 0%	0 0%	0 0%
Salivary gland changes/saliva	0 0%	1 0.1%	0 0%	0 0%	0 0%	0 0%
Secondary Malignancy-poss rel to cancer Tx	2 0.3%	2 0.3%	4 0.6%	3 0.5%	1 0.4%	0 0%
Seizure	0 0%	1 0.1%	1 0.1%	1 0.2%	0 0%	1 0.3%
Seroma	0 0%	0 0%	2 0.3%	0 0%	0 0%	0 0%
Sodium, serum-high (hypernatremia)	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Sodium, serum-low (hyponatremia)	7 1.1%	4 0.6%	5 0.7%	4 0.6%	1 0.4%	3 1%
Somnolence/depressed level of consciousness	2 0.3%	1 0.1%	0 0%	1 0.2%	0 0%	2 0.7%
Sudden death	2 0.3%	0 0%	0 0%	0 0%	0 0%	0 0%
Syncope (fainting)	5 0.8%	5 0.7%	7 1%	5 0.8%	5 1.8%	7 2.4%
Syndromes-Other	0 0%	2 0.3%	1 0.1%	0 0%	0 0%	0 0%
Taste alteration (dysgeusia)	1 0.2%	0 0%	2 0.3%	0 0%	0 0%	0 0%
Thrombosis/embolism (vascular access-related)	9 1.4%	18 2.6%	10 1.5%	6 0.9%	1 0.4%	4 1.4%
Thrombosis/thrombus/embolism	10 1.5%	7 1%	9 1.3%	8 1.3%	3 1.1%	4 1.4%
Ulcer, GI - Esophagus	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Ulcer, GI - Rectum	0 0%	0 0%	0 0%	0 0%	1 0.4%	0 0%
Uric acid, serum-high (hyperuricemia)	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Urticaria (hives, welts, wheals)	1 0.2%	0 0%	0 0%	0 0%	0 0%	1 0.3%
Vaginitis (not due to infection)	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%
Valvular heart disease	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Vasovagal episode	0 0%	0 0%	1 0.1%	0 0%	0 0%	0 0%
Ventricular arrhythmia - PVCs	1 0.2%	0 0%	0 0%	0 0%	0 0%	0 0%
Ventricular arrhythmia - Ventricular tachycardia	1 0.2%	1 0.1%	1 0.1%	0 0%	0 0%	0 0%
Viral hepatitis	1 0.2%	0 0%	0 0%	0 0%	0 0%	1 0.3%
Vision-blurred vision	1 0.2%	0 0%	1 0.1%	2 0.3%	0 0%	0 0%
Voice changes/dysarthria	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.3%
Vomiting	31 4.7%	29 4.2%	38 5.6%	17 2.7%	8 2.9%	6 2%
Watery eye (epiphora, tearing)	0 0%	2 0.3%	0 0%	0 0%	0 0%	0 0%
Weight loss	2 0.3%	2 0.3%	1 0.1%	1 0.2%	0 0%	2 0.7%
Wound complication, non-infectious	0 0%	1 0.1%	1 0.1%	0 0%	1 0.4%	0 0%

4. Secondary Outcome

Title	Disease-free Survival Comparison Between 2 Treatments in HR-positive, HER-2 Negative Group
Description	Disease-free survival (DFS) defined as time from registration (randomization assignment) to first instance of disease recurrence (local, regional, or distant), new breast primary tumor, or death as a result of any cause. The results are entered as disease free survival at year 5.
Time Frame	Biomarkers were measured by gene expression analysis before study entry. DFS were measured every 6 months for 5 years

Outcome Measure Data

Analysis Population Description
Patients with HR-positive, HER-2 negative at baseline in each arm were included in this analysis. Arm V and Arm VI were reopened under a new revised protocol and the data were not mature. And the results for Arm V and Arm VI will be reported in a subsequent publication.

Arm/Group Title	Arm I	Arm II	Arm III	Arm IV
Arm/Group 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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV
Measure Participants	375	370	373	362
Number (95% Confidence Interval) [percentage of participants]	82 12.3%	82 12%	86 12.6%	85 13.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Overall treatment differences.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.67
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Test of interaction of two treatments: AC and paclitaxel.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.42
	Comments
	Method	Log Rank
	Comments

5. Secondary Outcome

Title	Overall Survival Comparison Between 2 Treatments in HR-positive, HER-2 Negative Group
Description	Overall survival defined as time from registration to death as result of any cause. Results were entered as overall survival rate at year 5.
Time Frame	Biomarkers were measured by gene expression analysis before study entry. OS was measured every 6 months for 5 years

Outcome Measure Data

Analysis Population Description
Patients with HR-positive, HER-negative at baseline in each arm were included in this analysis. Arm V and Arm VI were reopened under a new revised protocol and the data were not mature. And the results for Arm V and Arm VI will be reported in a subsequent publication.

Arm/Group Title	Arm I	Arm II	Arm III	Arm IV
Arm/Group 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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV
Measure Participants	375	370	373	362
Number (95% Confidence Interval) [percentage of participants]	91 13.7%	92 13.5%	91 13.4%	90 14.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Test of overall treatment differences.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.90
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Test of interaction of two treatments: AC and paclitaxel.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.52
	Comments
	Method	Log Rank
	Comments

6. Secondary Outcome

Title	Disease-free Survival Comparison Between 2 Treatments in HR-negative, HER-2 Negative Group
Description	Disease-free survival (DFS) defined as time from registration (randomization assignment) to first instance of disease recurrence (local, regional, or distant), new breast primary tumor, or death as a result of any cause. The results are entered as disease free survival at year 5.
Time Frame	Biomarkers were measured by gene expression analysis before study entry. DFS was measured every 6 months for 5 years

Outcome Measure Data

Analysis Population Description
Patients with HR-negative, HER-2 negative at baseline in each arm were included in this analysis. Arm V and Arm VI were reopened under a new revised protocol and the data were not mature. And the results for Arm V and Arm VI will be reported in a subsequent publication.

Arm/Group Title	Arm I	Arm II	Arm III	Arm IV
Arm/Group 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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV
Measure Participants	153	185	180	162
Number (95% Confidence Interval) [percentage of participants]	83 12.5%	71 10.4%	72 10.6%	75 11.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Test of overall treatment differences.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.076
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Test of interaction of two treatments: AC and paclitaxel.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	Log Rank
	Comments

7. Secondary Outcome

Title	Overall Survival Comparison Between 2 Treatments in HR-negative, HER-2 Negative Group
Description	Overall survival defined as time from registration to death as result of any cause. Results were entered as overall survival rate at year 5.
Time Frame	Biomarkers were measured by gene expression analysis before study entry. OS was measured every 6 months for 5 years

Outcome Measure Data

Analysis Population Description
Patients with HR-negative, HER2-negative at baseline in each arm were included in this analysis. Arm V and Arm VI were reopened under a new revised protocol and the data were not mature. And the results for Arm V and Arm VI will be reported in a subsequent publication.

Arm/Group Title	Arm I	Arm II	Arm III	Arm IV
Arm/Group 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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV
Measure Participants	153	185	180	162
Number (95% Confidence Interval) [percentage of participants]	85 12.8%	76 11.1%	78 11.5%	82 12.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Test of overall treatment differences.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.062
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Test of interaction of two treatments: AC and paclitaxel.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	Log Rank
	Comments

8. Secondary Outcome

Title	Disease-free Survival Comparison Between 2 Treatments in HER2-positive Group
Description	Disease-free survival (DFS) defined as time from registration (randomization assignment) to first instance of disease recurrence (local, regional, or distant), new breast primary tumor, or death as a result of any cause. The results are entered as disease free survival at year 5.
Time Frame	Biomarkers were measured by gene expression analysis before study entry. DFS was measured every 6 months for 5 years

Outcome Measure Data

Analysis Population Description
Patients with HER2-positive at baseline in each arm were included in this analysis. One patient in Arm II with no follow-up was excluded. Arm V and Arm VI were reopened under a new revised protocol and the data were not mature. And the results for Arm V and Arm VI will be reported in a subsequent publication.

Arm/Group Title	Arm I	Arm II	Arm III	Arm IV
Arm/Group 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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV
Measure Participants	125	122	118	109
Number (95% Confidence Interval) [percentage of participants]	85 12.8%	83 12.2%	82 12%	80 12.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Test of overall treatment differences.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Test of interaction two treatments: AC and paclitaxel.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	Log Rank
	Comments

9. Secondary Outcome

Title	Overall Survival Comparison Between 2 Treatments in HER-2 Positive Group.
Description	Overall survival defined as time from registration to death as result of any cause. Results were entered as overall survival rate at year 5.
Time Frame	Biomarkers were measured by gene expression analysis before study entry. OS was measured every 6 months for 5 years

Outcome Measure Data

Analysis Population Description
Patients with HER2-positive at baseline in each arm were included in this analysis. One patient in Arm II with no follow-up was excluded. Arm V and Arm VI were reopened under a new revised protocol and the data were not mature. And the results for Arm V and Arm VI will be reported in a subsequent publication.

Arm/Group Title	Arm I	Arm II	Arm III	Arm IV
Arm/Group 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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(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. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV	(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III. pegfilgrastim: Given IV AC regimen: Given IV cyclophosphamide: Given IV doxorubicin hydrochloride: Given IV paclitaxel: Given IV
Measure Participants	125	122	118	109
Number (95% Confidence Interval) [percentage of participants]	94 14.2%	89 13%	89 13.1%	88 13.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Test of overall treatment differences
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.40
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I, Arm II, Arm III, Arm IV
	Comments	Test of interaction of two treatments: AC and paclitaxel.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments

Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Log Rank
	Comments

Adverse Events

	ARM I		ARM II		ARM III		ARM IV		ARM V		ARM VI
Time Frame	Toxicity assessment was evaluated every 4 weeks while on protocol therapy.
Adverse Event Reporting Description

Arm/Group Title	ARM I		ARM II		ARM III		ARM IV		ARM V		ARM VI
Arm/Group 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.		(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.		(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.		(closed 11/10/10) Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III.		Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. 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.		(reopened in 12/2010) Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 4 courses. Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses. Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	ARM I		ARM II		ARM III		ARM IV		ARM V		ARM VI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/654 (1.5%)		8/663 (1.2%)		17/674 (2.5%)		9/624 (1.4%)		5/275 (1.8%)		8/291 (2.7%)
Blood and lymphatic system disorders
Blood/Bone Marrow-Other	1/654 (0.2%)		0/663 (0%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
DIC (disseminated intravascular coagulation)	1/654 (0.2%)		0/663 (0%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Febrile neutropenia	0/654 (0%)		0/663 (0%)		0/674 (0%)		0/624 (0%)		1/275 (0.4%)		2/291 (0.7%)
Cardiac disorders
Cardiac-ischemia/infarction	0/654 (0%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Conduction abnormality - Asystole	0/654 (0%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Left ventricular diastolic dysfunction	1/654 (0.2%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Left ventricular systolic dysfunction	1/654 (0.2%)		0/663 (0%)		0/674 (0%)		0/624 (0%)		1/275 (0.4%)		0/291 (0%)
Myocarditis	0/654 (0%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Pericardial effusion (non-malignant)	0/654 (0%)		0/663 (0%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		1/291 (0.3%)
Ventricular arrhythmia - PVCs	1/654 (0.2%)		0/663 (0%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
General disorders
Constitutional Symptoms-Other	0/654 (0%)		1/663 (0.2%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Death - Multi-organ failure	1/654 (0.2%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Death not associated with CTCAE term - Death NOS	0/654 (0%)		0/663 (0%)		0/674 (0%)		1/624 (0.2%)		0/275 (0%)		1/291 (0.3%)
Hepatobiliary disorders
Liver dysfunction/failure (clinical)	1/654 (0.2%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Infections and infestations
Inf (clin/microbio) w/Gr 3-4 neuts - Lung	1/654 (0.2%)		1/663 (0.2%)		0/674 (0%)		2/624 (0.3%)		0/275 (0%)		0/291 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Blood	1/654 (0.2%)		0/663 (0%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Lung	0/654 (0%)		0/663 (0%)		0/674 (0%)		1/624 (0.2%)		0/275 (0%)		0/291 (0%)
Inf w/normal ANC or Gr 1-2 neutrophils - Soft tiss	0/654 (0%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Infection with unknown ANC - Blood	0/654 (0%)		0/663 (0%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		1/291 (0.3%)
Infection with unknown ANC - Skin (cellulitis)	0/654 (0%)		0/663 (0%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		1/291 (0.3%)
Injury, poisoning and procedural complications
Thrombosis/embolism (vascular access-related)	0/654 (0%)		1/663 (0.2%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Investigations
ALT, SGPT (serum glutamic pyruvic transaminase)	0/654 (0%)		0/663 (0%)		2/674 (0.3%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
AST, SGOT	0/654 (0%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Bilirubin (hyperbilirubinemia)	0/654 (0%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Cardiac troponin I (cTnI)	0/654 (0%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Neutrophils/granulocytes (ANC/AGC)	0/654 (0%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		3/275 (1.1%)		0/291 (0%)
Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)	0/654 (0%)		0/663 (0%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		1/291 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplasia	0/654 (0%)		1/663 (0.2%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Secondary Malignancy-poss rel to cancer Tx	2/654 (0.3%)		1/663 (0.2%)		4/674 (0.6%)		3/624 (0.5%)		1/275 (0.4%)		0/291 (0%)
Nervous system disorders
CNS cerebrovascular ischemia	0/654 (0%)		0/663 (0%)		0/674 (0%)		1/624 (0.2%)		0/275 (0%)		0/291 (0%)
Seizure	0/654 (0%)		0/663 (0%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		1/291 (0.3%)
Somnolence/depressed level of consciousness	0/654 (0%)		0/663 (0%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		1/291 (0.3%)
Psychiatric disorders
Confusion	0/654 (0%)		1/663 (0.2%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome (ARDS)	1/654 (0.2%)		0/663 (0%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Dyspnea (shortness of breath)	0/654 (0%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Pleural effusion (non-malignant)	0/654 (0%)		1/663 (0.2%)		0/674 (0%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Pneumonitis/pulmonary infiltrates	0/654 (0%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Pulmonary/Upper Respiratory-Other	1/654 (0.2%)		1/663 (0.2%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Vascular disorders
Hypotension	0/654 (0%)		0/663 (0%)		1/674 (0.1%)		0/624 (0%)		0/275 (0%)		0/291 (0%)
Thrombosis/thrombus/embolism	1/654 (0.2%)		2/663 (0.3%)		2/674 (0.3%)		1/624 (0.2%)		0/275 (0%)		0/291 (0%)
Other (Not Including Serious) Adverse Events
	ARM I		ARM II		ARM III		ARM IV		ARM V		ARM VI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	381/654 (58.3%)		412/663 (62.1%)		389/674 (57.7%)		391/624 (62.7%)		131/275 (47.6%)		126/291 (43.3%)
Blood and lymphatic system disorders
Febrile neutropenia	49/654 (7.5%)		9/663 (1.4%)		38/674 (5.6%)		20/624 (3.2%)		15/275 (5.5%)		12/291 (4.1%)
Hemoglobin	87/654 (13.3%)		48/663 (7.2%)		101/674 (15%)		47/624 (7.5%)		21/275 (7.6%)		19/291 (6.5%)
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam) - Oral cavity	17/654 (2.6%)		56/663 (8.4%)		23/674 (3.4%)		57/624 (9.1%)		4/275 (1.5%)		3/291 (1%)
Mucositis/stomatitis (functional/symp) - Oral cav	11/654 (1.7%)		38/663 (5.7%)		28/674 (4.2%)		40/624 (6.4%)		1/275 (0.4%)		6/291 (2.1%)
Nausea	50/654 (7.6%)		40/663 (6%)		53/674 (7.9%)		33/624 (5.3%)		9/275 (3.3%)		9/291 (3.1%)
Vomiting	31/654 (4.7%)		29/663 (4.4%)		38/674 (5.6%)		17/624 (2.7%)		8/275 (2.9%)		6/291 (2.1%)
General disorders
Fatigue (asthenia, lethargy, malaise)	77/654 (11.8%)		59/663 (8.9%)		87/674 (12.9%)		65/624 (10.4%)		20/275 (7.3%)		14/291 (4.8%)
Investigations
Leukocytes (total WBC)	128/654 (19.6%)		98/663 (14.8%)		157/674 (23.3%)		128/624 (20.5%)		38/275 (13.8%)		34/291 (11.7%)
Lymphopenia	24/654 (3.7%)		31/663 (4.7%)		26/674 (3.9%)		32/624 (5.1%)		15/275 (5.5%)		18/291 (6.2%)
Neutrophils/granulocytes (ANC/AGC)	174/654 (26.6%)		156/663 (23.5%)		217/674 (32.2%)		201/624 (32.2%)		54/275 (19.6%)		65/291 (22.3%)
Musculoskeletal and connective tissue disorders
Pain - Bone	10/654 (1.5%)		36/663 (5.4%)		15/674 (2.2%)		9/624 (1.4%)		15/275 (5.5%)		1/291 (0.3%)
Pain - Joint	39/654 (6%)		40/663 (6%)		21/674 (3.1%)		12/624 (1.9%)		11/275 (4%)		5/291 (1.7%)
Pain - Muscle	42/654 (6.4%)		48/663 (7.2%)		21/674 (3.1%)		11/624 (1.8%)		10/275 (3.6%)		5/291 (1.7%)
Nervous system disorders
Neuropathy: sensory	107/654 (16.4%)		101/663 (15.2%)		76/674 (11.3%)		56/624 (9%)		45/275 (16.4%)		25/291 (8.6%)
Skin and subcutaneous tissue disorders
Rash: hand-foot skin reaction	19/654 (2.9%)		95/663 (14.3%)		16/674 (2.4%)		94/624 (15.1%)		3/275 (1.1%)		4/291 (1.4%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

Name/Title	Breast Committee Statistician
Organization	SWOG Statistical Center
Phone	206-667-4623
Email	jmiao@fredhutch.org

Responsible Party:

Southwest Oncology Group

ClinicalTrials.gov Identifier:

NCT00070564

Other Study ID Numbers:

CDR0000334899
S0221
U10CA032102

First Posted:

Oct 7, 2003

Last Update Posted:

Jan 21, 2022

Last Verified:

Jan 1, 2022

S0221 Adjuvant Doxorubicin, Cyclophosphamide, and Paclitaxel in Treating Patients With Breast Cancer

Study Details

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Detailed Description

OBJECTIVES:

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

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DISEASE CHARACTERISTICS:

PATIENT CHARACTERISTICS:

PRIOR CONCURRENT THERAPY:

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Study Documents (Full-Text)

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Study Results

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Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Statistical Analysis 5

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Statistical Analysis 5

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Adverse Events

All Cause Mortality

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Results Point of Contact