Comparison of Combination Chemotherapy Regimens in Treating Older Women Who Have Undergone Surgery for 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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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|
- Relapse-free Survival Rates at 2.4 Years [ Time Frame: randomization until date of first event, or date last known to be event free if no event was reported (up to 5 years) ] [ Designated as safety issue: No ]Percentage of participants who were alive and relapse-free at time of analysis were counted as "Alive without relapse" at 2.4 years. Participants who had a first local recurrence, first distant metastasis or death from any cause were counted as "relapse, first occurrence". These rates were estimated using the Kaplan Meier method
- Overall Survival Rate at 2.4 Years [ Time Frame: Time from registration to death (up to 15 years) ] [ Designated as safety issue: No ]Percentage of patients who were alive at 2.4 years. This rate was estimated using the Kaplan Meier method.
- Number of Participants With Grade 3, 4 or 5 Adverse Event at Least Possibly Related to Treatment. [ Time Frame: Reported during protocol treatment after each cycle ] [ Designated as safety issue: Yes ]
The National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 2.0 was used to evaluate toxicity.
Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death.
|Study Start Date:||September 2001|
|Study Completion Date:||November 2012|
|Primary Completion Date:||May 2008 (Final data collection date for primary outcome measure)|
Active Comparator: Standard Chemotherapy
Patient/Physician choice of cyclophosphamide + MTX + 5-FU
Cyclophosphamide + doxorubicin
Drug: Standard Treatment
Cyclophosphamide 100 mg/sq m PO d 1-14 + MTX 40 mg/sq m IV push d 1 & 8 and 5-FU 600 mg/sq m IV push d 1 & 8 q 28 days for 6 cycles OR doxorubicin 60 mg/sq m IV d 1 + cyclophosphamide 600 mg/sq m IV d 1 q 21 d for 4 cycles
Other Name: doxorubicin = adriamycin
Treatment with capecitabine
2000 mg/sq m PO d 1-14, 7 day rest then repeat for a total of 6 cycles
- Compare the effectiveness of adjuvant chemotherapy comprising standard cyclophosphamide, methotrexate, and fluorouracil (CMF) or doxorubicin and cyclophosphamide (AC) vs oral capecitabine, in terms of disease-free and overall survival, in elderly women with operable adenocarcinoma of the breast.
- Compare the quality of life and physical functioning of patients treated with these regimens.
- Compare the toxicity of these regimens in these patients.
- Evaluate the adherence of older patients to an oral chemotherapy regimen.
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.
- Group A (CMF): Patients receive oral cyclophosphamide (CTX) daily on days 1-14 and methotrexate IV and fluorouracil IV on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
- Group B (AC): Patients receive doxorubicin IV and CTX IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00024102
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|Study Chair:||Hyman B. Muss, MD||University of North Carolina|