Combination Chemotherapy With or Without Colony-stimulating Factors in Treating Women With Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Biological: epoetin alfaBiological: filgrastim
- Registration Number
- NCT00014222
- Lead Sponsor
- NCIC Clinical Trials Group
- Brief Summary
RATIONALE:
1. . To compare the effects on breast cancer of three different combinations of drugs which are commonly used to treat this disease.
2. . It is not yet known which treatment regimen is most effective for breast cancer.
PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy given with or without epoetin alfa in treating women who have undergone surgery for stage I, stage II, or stage III breast cancer.
- Detailed Description
OBJECTIVES:
Primary
* Compare the disease-free survival of premenopausal or early postmenopausal women with previously resected node positive or high-risk node negative stage I-IIIB breast cancer treated with cyclophosphamide, epirubicin, and fluorouracil vs cyclophosphamide, epirubicin, filgrastim (G-CSF), and epoetin alfa followed by paclitaxel vs cyclophosphamide and doxorubicin followed by paclitaxel.
Secondary
* Compare the overall survival of patients treated with these regimens.
* Compare the rate of toxic effects of these regimens in this patient population.
* Compare the quality of life of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of positive nodes (0 vs 1-3 vs 4-10 vs more than 10), type of prior surgery (total vs partial mastectomy), and estrogen receptor status (positive vs negative). Patients are randomized to one of three treatment arms.
* Arm I: Patients receive epirubicin IV and fluorouracil IV on days 1 and 8 and oral cyclophosphamide on days 1-14. Treatment repeats every 28 days for 6 courses.
* Arm II: Patients receive epirubicin IV and cyclophosphamide IV on day 1 and filgrastim (G-CSF) subcutaneously (SC) on days 2-13. Patients with a hemoglobin \< 13.0 g/dL also receive epoetin alfa SC once weekly beginning within 1 week after the start of therapy and continuing as needed. Treatment repeats every 14 days for 6 courses. Beginning 21 days after completion of epirubicin and cyclophosphamide, patients receive paclitaxel IV over 3 hours on day 1 and G-CSF and epoetin alfa as above. Treatment repeats every 21 days for 4 courses.
* Arm III: Patients receive doxorubicin IV over 15 minutes and cyclophosphamide IV over 15 minutes on day 1. Treatment repeats every 21 days for 4 courses. Beginning 21 days after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel as in arm II. Treatment in all arms continues in the absence of disease progression or unacceptable toxicity.
All receptor positive patients receive oral tamoxifen or anastrozole (if tamoxifen is contraindicated) for 5 years after completion of chemotherapy.
Quality of life is assessed at baseline, day 1 of cycles 2, 3 4 and 6 (arm I), days 1 of cycles 3 and and day 1 of cycles 1 and 4 of paclitaxel (arm II), day 1 of cycles 2 and 3, day 1 of cycles 1 and 4 of paclitaxel, (arm III), 9 months, 12 months, and then annually thereafter until 5 years
Patients are followed at 9 months, 12 months, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 2,100 patients (700 per treatment arm) will be accrued for this study within 4 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 2104
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: CEF cyclophosphamide 6 cycles - q 28 days (6 months) - Cyclophosphamide 75 mg/m2 - po - Days 1-14 - Epirubicin 60 mg/m2 - IV - Days 1 and 8 - 5 Fluorouracil: 500mg/m2 - IV - Days 1 and 8 + Continuous Antibiotic Prophylaxis with Cotrimoxazole 960 mg (i.e.2x480 mg tablets) po-bid or Ciprofloxacin 500 mg - po-bid Arm 1: CEF epirubicin hydrochloride 6 cycles - q 28 days (6 months) - Cyclophosphamide 75 mg/m2 - po - Days 1-14 - Epirubicin 60 mg/m2 - IV - Days 1 and 8 - 5 Fluorouracil: 500mg/m2 - IV - Days 1 and 8 + Continuous Antibiotic Prophylaxis with Cotrimoxazole 960 mg (i.e.2x480 mg tablets) po-bid or Ciprofloxacin 500 mg - po-bid Arm 1: CEF fluorouracil 6 cycles - q 28 days (6 months) - Cyclophosphamide 75 mg/m2 - po - Days 1-14 - Epirubicin 60 mg/m2 - IV - Days 1 and 8 - 5 Fluorouracil: 500mg/m2 - IV - Days 1 and 8 + Continuous Antibiotic Prophylaxis with Cotrimoxazole 960 mg (i.e.2x480 mg tablets) po-bid or Ciprofloxacin 500 mg - po-bid Arm 2: EC/T epoetin alfa 6 cycles - q 14 days (3 months) - Epirubicin 120 mg/m2 - IV - Day 1 - Cyclophosphamide 830 mg/m2 - IV - Day 1 - Filgrastim 5μg/kg/d - SC - Days 2 - 13 + Epoetin Alfa 40,000 IU - SC - once weekly (to begin within 1 week after start of protocol therapy as needed) 21 days from last administration of EC (EC/T) 4 cycles - q 21 days (3 months) - Adriamycin 60 mg/m2 - IV - Day 1 - Cyclophosphamide 600 mg/m2 - IV - Day 1 - 21 days from last administration of AC 4 cycles - q 21 days (3 months) - Paclitaxel 175 mg/m2 IV 3 hour infusion Arm 2: EC/T filgrastim 6 cycles - q 14 days (3 months) - Epirubicin 120 mg/m2 - IV - Day 1 - Cyclophosphamide 830 mg/m2 - IV - Day 1 - Filgrastim 5μg/kg/d - SC - Days 2 - 13 + Epoetin Alfa 40,000 IU - SC - once weekly (to begin within 1 week after start of protocol therapy as needed) 21 days from last administration of EC (EC/T) 4 cycles - q 21 days (3 months) - Adriamycin 60 mg/m2 - IV - Day 1 - Cyclophosphamide 600 mg/m2 - IV - Day 1 - 21 days from last administration of AC 4 cycles - q 21 days (3 months) - Paclitaxel 175 mg/m2 IV 3 hour infusion Arm 3: AC/T cyclophosphamide 4 cycles - q 21 days (3 months) - Adriamycin 60 mg/m2 - IV - Day 1 - Cyclophosphamide 600 mg/m2 - IV - Day 1 21 days from last administration of AC 4 cycles - q 21 days (3 months) - Paclitaxel 175 mg/m2 IV 3 hour infusion Arm 3: AC/T doxorubicin hydrochloride 4 cycles - q 21 days (3 months) - Adriamycin 60 mg/m2 - IV - Day 1 - Cyclophosphamide 600 mg/m2 - IV - Day 1 21 days from last administration of AC 4 cycles - q 21 days (3 months) - Paclitaxel 175 mg/m2 IV 3 hour infusion Arm 3: AC/T paclitaxel 4 cycles - q 21 days (3 months) - Adriamycin 60 mg/m2 - IV - Day 1 - Cyclophosphamide 600 mg/m2 - IV - Day 1 21 days from last administration of AC 4 cycles - q 21 days (3 months) - Paclitaxel 175 mg/m2 IV 3 hour infusion Arm 2: EC/T doxorubicin hydrochloride 6 cycles - q 14 days (3 months) - Epirubicin 120 mg/m2 - IV - Day 1 - Cyclophosphamide 830 mg/m2 - IV - Day 1 - Filgrastim 5μg/kg/d - SC - Days 2 - 13 + Epoetin Alfa 40,000 IU - SC - once weekly (to begin within 1 week after start of protocol therapy as needed) 21 days from last administration of EC (EC/T) 4 cycles - q 21 days (3 months) - Adriamycin 60 mg/m2 - IV - Day 1 - Cyclophosphamide 600 mg/m2 - IV - Day 1 - 21 days from last administration of AC 4 cycles - q 21 days (3 months) - Paclitaxel 175 mg/m2 IV 3 hour infusion Arm 2: EC/T cyclophosphamide 6 cycles - q 14 days (3 months) - Epirubicin 120 mg/m2 - IV - Day 1 - Cyclophosphamide 830 mg/m2 - IV - Day 1 - Filgrastim 5μg/kg/d - SC - Days 2 - 13 + Epoetin Alfa 40,000 IU - SC - once weekly (to begin within 1 week after start of protocol therapy as needed) 21 days from last administration of EC (EC/T) 4 cycles - q 21 days (3 months) - Adriamycin 60 mg/m2 - IV - Day 1 - Cyclophosphamide 600 mg/m2 - IV - Day 1 - 21 days from last administration of AC 4 cycles - q 21 days (3 months) - Paclitaxel 175 mg/m2 IV 3 hour infusion Arm 2: EC/T paclitaxel 6 cycles - q 14 days (3 months) - Epirubicin 120 mg/m2 - IV - Day 1 - Cyclophosphamide 830 mg/m2 - IV - Day 1 - Filgrastim 5μg/kg/d - SC - Days 2 - 13 + Epoetin Alfa 40,000 IU - SC - once weekly (to begin within 1 week after start of protocol therapy as needed) 21 days from last administration of EC (EC/T) 4 cycles - q 21 days (3 months) - Adriamycin 60 mg/m2 - IV - Day 1 - Cyclophosphamide 600 mg/m2 - IV - Day 1 - 21 days from last administration of AC 4 cycles - q 21 days (3 months) - Paclitaxel 175 mg/m2 IV 3 hour infusion
- Primary Outcome Measures
Name Time Method Disease Free Survival 13 years Disease free survival was defined as the time from randomization to the time of recurrence of the primary disease. Local or nodal recurrence and metastatic disease were considered a recurrence of the primary tumour. Patients who had contralateral breast cancer or a second primary malignancy, or died from some cause other than disease were censored as relapse-free at the time of death. Patients who had not relapsed were censored at longest follow-up or at non-breast cancer death. As required, adjudication was used to assess reports of recurrence.
- Secondary Outcome Measures
Name Time Method Overall Survival 13 years Overall survival was defined as the time from randomization to the time of death from any cause, with censoring at longest follow-up.
Trial Locations
- Locations (78)
Sparks-Arkansas Oklahoma Cancer Treatment Centre
🇺🇸Fort Smith, Arkansas, United States
Maine Center for Cancer Medicine and Blood Disorders
🇺🇸Scarborough, Maine, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
ECU School of Medicine, Leo Jenkins Cancer Center
🇺🇸Greenville, North Carolina, United States
Odette Cancer Centre
🇨🇦Toronto, Ontario, Canada
Lakeridge Health Oshawa
🇨🇦Oshawa, Ontario, Canada
Mount Sinai Hospital
🇨🇦Toronto, Ontario, Canada
Trillium Health Centre - West Toronto
🇨🇦Toronto, Ontario, Canada
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
Florida Oncology Associates
🇺🇸Orange Park, Florida, United States
Columbia-Capitol Comprehensive Care Clinics
🇺🇸Jefferson City, Missouri, United States
University of Colorado Cancer Centre
🇺🇸Aurora, Colorado, United States
Scripps Cancer Center
🇺🇸La Jolla, California, United States
Consultants in Blood Disorders and Cancer
🇺🇸Louisville, Kentucky, United States
Sibley Memorial Hospital, Oncology Research
🇺🇸Washington, District of Columbia, United States
Atlantic Health Sciences Corporation
🇨🇦Saint John, New Brunswick, Canada
Greenwich Hospital - Bendheim Cancer Center
🇺🇸Greenwich, Connecticut, United States
Saint Louis University Hospital
🇺🇸Saint Louis, Missouri, United States
St. Luke's Cancer Care Centre
🇺🇸Duluth, Minnesota, United States
Dr. H. Bliss Murphy Cancer Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
Winthrop University Hospital Onc/Hem
🇺🇸Mineola, New York, United States
Northeast Cancer Center Health Sciences
🇨🇦Sudbury, Ontario, Canada
Our Lady of Mercy Medical Center
🇺🇸Bronx, New York, United States
London Regional Cancer Program
🇨🇦London, Ontario, Canada
Hopital Maisonneuve-Rosemont
🇨🇦Montreal, Quebec, Canada
CHUM - Hopital Notre-Dame
🇨🇦Montreal, Quebec, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Arlington-Fairfax Hematology Oncology P.C.
🇺🇸Arlington, Virginia, United States
Thunder Bay Regional Health Science Centre
🇨🇦Thunder Bay, Ontario, Canada
Algoma District Cancer Program
🇨🇦Sault Ste. Marie, Ontario, Canada
The Scarborough Hospital
🇨🇦Scarborough, Ontario, Canada
Hopital Charles LeMoyne
🇨🇦Greenfield Park, Quebec, Canada
Suburban Hospital Cancer Program
🇺🇸Bethesda, Maryland, United States
Saint Joseph Medical Center, Cancer Care Program
🇺🇸Towson, Maryland, United States
University of Minnesota Cancer Centre
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Oncology/Hematology Care, Inc.
🇺🇸Cincinnati, Ohio, United States
PEI Cancer Treatment Centre,Queen Elizabeth Hospital
🇨🇦Charlottetown, Prince Edward Island, Canada
BCCA - Fraser Valley Cancer Centre
🇨🇦Surrey, British Columbia, Canada
The Moncton Hospital
🇨🇦Moncton, New Brunswick, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Cancer Centre of Southeastern Ontario at Kingston
🇨🇦Kingston, Ontario, Canada
The Royal Victoria Hospital
🇨🇦Barrie, Ontario, Canada
Ottawa Health Research Institute - General Division
🇨🇦Ottawa, Ontario, Canada
Grand River Regional Cancer Centre
🇨🇦Kitchener, Ontario, Canada
Univ. Health Network-Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
CHUM - Hotel Dieu du Montreal
🇨🇦Montreal, Quebec, Canada
Queens Medical Associates, PC
🇺🇸Fresh Meadows, New York, United States
Hematology Oncology Services of Arkansas
🇺🇸Little Rock, Arkansas, United States
Comprehensive Cancer Care Centre at Boca Raton
🇺🇸Boca Raton, Florida, United States
Therapy Associates, Inc., Hematology/Oncology
🇺🇸Evansville, Indiana, United States
CHRISTUS Schumpert Medical Center - Hem/Onc Clinic
🇺🇸Shreveport, Louisiana, United States
Associates in Oncology/Hematology
🇺🇸Rockville, Maryland, United States
Maine General Medical Center
🇺🇸Waterville, Maine, United States
Baystate Regional Cancer Program
🇺🇸Springfield, Massachusetts, United States
Creighton University Cancer Centre
🇺🇸Omaha, Nebraska, United States
Advanced Oncology Associates
🇺🇸Armonk, New York, United States
Hematology Oncol. Associates Rockland
🇺🇸Nyack, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Lone Star Oncology Consultants, PA
🇺🇸Austin, Texas, United States
Pottstown Memorial Regional Cancer Centre
🇺🇸Pottstown, Pennsylvania, United States
Santee Hematology Oncology
🇺🇸Sumter, South Carolina, United States
University Oncology and Hematology Associates
🇺🇸Chattanooga, Tennessee, United States
Center for Oncology Research and Treatment
🇺🇸Dallas, Texas, United States
Northern Utah Associates
🇺🇸Ogden, Utah, United States
BCCA - Cancer Centre for the Southern Interior
🇨🇦Kelowna, British Columbia, Canada
BCCA - Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
QEII Health Sciences Center
🇨🇦Halifax, Nova Scotia, Canada
Juravinski Cancer Centre at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Lexington Oncology Assts./Central Baptist Hospital
🇺🇸Lexington, Kentucky, United States
Staten Island University Hospital
🇺🇸Staten Island, New York, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Niagara Health System
🇨🇦St. Catharines, Ontario, Canada
Windsor Regional Cancer Centre
🇨🇦Windsor, Ontario, Canada
Willis-Knighton Cancer Center
🇺🇸Shreveport, Louisiana, United States