High-Dose Combination Chemotherapy Plus Peripheral Stem Cell Transplantation Compared With Standard Combination Chemotherapy in Treating Women With High-Risk Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Drug: CMF regimenBiological: filgrastimProcedure: peripheral blood stem cell transplantationRadiation: low-LET electron therapyRadiation: low-LET photon therapy
- Registration Number
- NCT00002784
- Lead Sponsor
- ETOP IBCSG Partners Foundation
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. It is not yet known if high-dose combination chemotherapy plus peripheral stem cell transplantation is more effective than standard combination chemotherapy for breast cancer.
PURPOSE: Randomized phase III trial to compare high-dose combination chemotherapy plus peripheral stem cell transplantation with standard combination chemotherapy in treating women with stage II or stage III breast cancer.
- Detailed Description
OBJECTIVES: I. Compare the survival, disease-free survival, and systemic disease-free survival of women with high-risk, operable stage II/III breast cancer treated with three courses of dose-intensive epirubicin/cyclophosphamide (EC) supported by granulocyte colony-stimulating factor (G-CSF) and G-CSF-mobilized peripheral blood stem cells vs. standard EC followed by cyclophosphamide/methotrexate/fluorouracil. II. Compare the toxicity, duration of quality-adjusted time without symptoms and toxicity, and quality of life associated with these two treatments. III. Evaluate the cost effectiveness of these two treatments.
OUTLINE: This is a randomized study. Patients are stratified by estrogen receptor status and menopausal status. Within 6 weeks of surgery, patients in the first group receive epirubicin (preferred) or doxorubicin plus cyclophosphamide every 3 weeks for 4 courses followed by conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) every 4 weeks for 3 courses. Patients in the second group undergo stem cell mobilization and harvest with granulocyte colony-stimulating factor (G-CSF) followed within 10 weeks of surgery by high-dose chemotherapy with epirubicin and cyclophosphamide followed by peripheral blood stem cell rescue and G-CSF. All patients receive adjuvant tamoxifen, and patients who underwent lumpectomy prior to entry are required to receive adjuvant radiotherapy (radiotherapy is optional for patients who underwent mastectomy prior to entry). Patients are followed every 3 months for 2 years, then q 6 months for 3 years, then yearly.
PROJECTED ACCRUAL: 210 patients will be accrued over 4 years to provide 195 evaluable patients.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 344
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard chemotherapy CMF regimen EC/AC x 4 followed by CMF x 3 and tamoxifen to 5 years after randomization. Standard chemotherapy cyclophosphamide EC/AC x 4 followed by CMF x 3 and tamoxifen to 5 years after randomization. Standard chemotherapy doxorubicin hydrochloride EC/AC x 4 followed by CMF x 3 and tamoxifen to 5 years after randomization. Standard chemotherapy epirubicin hydrochloride EC/AC x 4 followed by CMF x 3 and tamoxifen to 5 years after randomization. Standard chemotherapy fluorouracil EC/AC x 4 followed by CMF x 3 and tamoxifen to 5 years after randomization. Standard chemotherapy methotrexate EC/AC x 4 followed by CMF x 3 and tamoxifen to 5 years after randomization. Standard chemotherapy tamoxifen citrate EC/AC x 4 followed by CMF x 3 and tamoxifen to 5 years after randomization. Standard chemotherapy low-LET electron therapy EC/AC x 4 followed by CMF x 3 and tamoxifen to 5 years after randomization. Standard chemotherapy low-LET photon therapy EC/AC x 4 followed by CMF x 3 and tamoxifen to 5 years after randomization. Dose-intensive EC filgrastim High-dose EC x 3 supported by peripheral blood progenitor cells and tamoxifen to 5 years after randomization. Dose-intensive EC mesna High-dose EC x 3 supported by peripheral blood progenitor cells and tamoxifen to 5 years after randomization. Dose-intensive EC tamoxifen citrate High-dose EC x 3 supported by peripheral blood progenitor cells and tamoxifen to 5 years after randomization. Dose-intensive EC peripheral blood stem cell transplantation High-dose EC x 3 supported by peripheral blood progenitor cells and tamoxifen to 5 years after randomization. Dose-intensive EC low-LET electron therapy High-dose EC x 3 supported by peripheral blood progenitor cells and tamoxifen to 5 years after randomization. Dose-intensive EC low-LET photon therapy High-dose EC x 3 supported by peripheral blood progenitor cells and tamoxifen to 5 years after randomization. Dose-intensive EC cyclophosphamide High-dose EC x 3 supported by peripheral blood progenitor cells and tamoxifen to 5 years after randomization.
- Primary Outcome Measures
Name Time Method Disease-free survival. 16 years after randomization. Time from randomization to recurrence (including recurrence isolated to the breast), metastasis, appearance of a second primary tumor, or death from any cause, whichever occurs first.
- Secondary Outcome Measures
Name Time Method Overall survival. 16 years after randomization. Time from randomization to death from any cause.
Toxicity. 5 years after randomization. Morbidity information was recorded using standard toxicity criteria.
Quality of life. 16 years after randomization. Quality of life was assessed using standard International Breast Cancer Study Group instruments.
Trial Locations
- Locations (11)
Queen Elizabeth Hospital
🇦🇺Adelaide, South Australia, Australia
Royal Prince Alfred Hospital, Sydney
🇦🇺Sydney, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Newcastle Mater Misericordiae Hospital
🇦🇺Newcastle, New South Wales, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Swiss Institute for Applied Cancer Research
🇨ðŸ‡Bern, Switzerland
Inselspital, Bern
🇨ðŸ‡Bern, Switzerland
Centre Hospitalier Universitaire Vaudois
🇨ðŸ‡Lausanne, Switzerland
Universitaetsspital
🇨ðŸ‡Zurich, Switzerland
Istituto Oncologico della Svizzera Italiana
🇨ðŸ‡Lugano, Switzerland
Kantonsspital - Saint Gallen
🇨ðŸ‡Saint Gallen, Switzerland