A Randomized Trial of Adjuvant Chemotherapy With Standard Regimens, Cyclophosphamide, Methotrexate and Fluorouracil - (CMF) or Doxorubicin and Cyclophosphamide - (AC), Versus Capecitabine in Women 65 Years and Older With Node Positive or Node-Negative Breast Cancer
A Randomized Trial of Adjuvant Chemotherapy With Standard Regimens, Cyclophosphamide, Methotrexate and Fluorouracil - (CMF) or Doxorubicin and Cyclophosphamide - (AC), Versus Capecitabine in Women 65 Years and Older With Node Positive or Node-Negative Breast Cancer
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them in different ways after surgery may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective in treating older women with breast cancer.
PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens to see how well they work in treating older women who have undergone surgery for breast cancer.
OBJECTIVES:
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (65 to 69 vs 70 to 80 vs over 80), performance status (0-1 vs 2), and HER2 status (positive vs negative vs unknown). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients with insufficient left ventricular ejection fraction (LVEF) are assigned to group A. Patients with normal LVEF are assigned to group A or B based on physician/patient choice.
Arm II: Patients receive oral capecitabine twice daily on days 1-14. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
Beginning within 12 weeks after treatment in arm I or II, patients with estrogen or progesterone receptor-positive disease receive oral tamoxifen or an aromatase inhibitor daily for 5 years.
Beginning 4-6 weeks after treatment in arm I or II, eligible patients who previously underwent breast conservation surgery undergo radiotherapy.
Quality of life is assessed at baseline; at 6 weeks (group B), 9 weeks (arm II), or 12 weeks (group A); and then at 1, 12, 18, and 24 months after study.
Drug adherence is assessed at 9 weeks during study (arm II).
Patients are followed at 1 month, every 6 months for 2 years, and then annually for 15 years.
PROJECTED ACCRUAL: A total of 600-1,800 patients (300-900 per treatment arm) will be accrued for this study within 2-6 years.
Patients with operable, histologically confirmed adenocarcinoma of the female breast.
TNM Stage per AJCC Cancer Staging Manual 6th edition:
Patients with HER2/neu positive, negative or unknown disease are eligible for this trial.
Patients whose tumors are HER2 positive by either immunohistochemistry 3+ staining or demonstrate gene amplification by FISH will be eligible to receive trastuzumab, as outlined in the protocol.
Age 65 years or older
Performance status 0-2 (Common Toxicity Criteria).
Prior treatment:
Surgical resection -
No prior chemotherapy for this malignancy.
Patients with a history of hypersensitivity to 5-FU or known dihydropyrimidine dehydrogenase (DPD) deficiency are not eligible to participate.
Patients may receive up to four weeks of tamoxifen therapy for this malignancy and still be eligible for study entry. Patients who received tamoxifen or raloxifene for purposes of chemoprevention (e.g., Breast Cancer Prevention Trial) or for other indications (including previous breast cancer) are eligible. Tamoxifen or raloxifene therapy should be discontinued before the patient is enrolled on this study.
Required Initial Laboratory Data:
Birmingham, Alabama 35294, United States
Tucson, Arizona 85724-5024, United States
Los Angeles, California 90089-9181, United States
Northridge, California 91328, United States
Oakland, California 94602, United States
Fort Lauderdale, Florida 33308, United States
Lakeland, Florida 33805, United States
Savannah, Georgia 31405, United States
Honolula, Hawaii 96813, United States
Chicago, Illinois 60611-3013, United States
Libertyville, Illinois 60048, United States
Olympia Fields, Illinois 60461, United States
Peoria, Illinois 61615, United States
Skokie, Illinois 60076, United States
Beech Grove, Indiana 46107, United States
Scarborough, Maine 04074, United States
Baltimore, Maryland 21201, United States
Baltimore, Maryland 21231-2410, United States
Boston, Massachusetts 02115, United States
Lowell, Massachusetts 01852, United States
Saint Joseph, Michigan 49085, United States
Southfield, Michigan 48075, United States
Lichfield, Minnesota 55355, United States
Maplewood, Minnesota 55109, United States
Minneapolis, Minnesota 55407, United States
Minneapolis, Minnesota 55455, United States
Robbinsdale, Minnesota 55422-2900, United States
Columbia, Missouri 65203, United States
Grand Island, Nebraska 68803, United States
Omaha, Nebraska 68198-6805, United States
Carson City, Nevada 89703, United States
Derry, New Hampshire 03038, United States
Marlton, New Jersey 08053, United States
Morristown, New Jersey 07962, United States
Toms River, New Jersey 08755, United States
Voorhees Township, New Jersey 08043, United States
Rochester, New York 14642, United States
The Bronx, New York 10456, United States
Greensboro, North Carolina 27403-1198, United States
Pinehurst, North Carolina 28374, United States
Wilmington, North Carolina 28401, United States
East Stroudsburg, Pennsylvania 18301, United States
Hershey, Pennsylvania 17033-0850, United States
Philadelphia, Pennsylvania 19107-5541, United States
Pittsburgh, Pennsylvania 15224-1791, United States
Upland, Pennsylvania 19013, United States
Wilkes-Barre, Pennsylvania 18711, United States
Charleston, South Carolina 29425, United States
Spartanburg, South Carolina 29303, United States
Sioux Falls, South Dakota 57117-5039, United States
Johnson City, Tennessee 37604, United States
Burlington, Vermont 05401, United States
Seattle, Washington 98122-4307, United States
Seattle, Washington 98195-6043, United States
Yakima, Washington 98902, United States
Elkhorn, Wisconsin 53121, United States
Green Bay, Wisconsin 54311, United States
La Crosse, Wisconsin 54601, United States
Manitowoc, Wisconsin 54221-1450, United States
Wausau, Wisconsin 54401, United States
Charlottetown, Prince Edward Island C1A 8T5, Canada