Breast Cancer Clinical Trial
S0221 Adjuvant Doxorubicin, Cyclophosphamide, and Paclitaxel in Treating Patients With Breast Cancer
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.
Full 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.
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 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.
Eligibility Criteria
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
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