Randomized Trial of High-dose Epirubicin and Cyclophosphamide x 3 Supported by Peripheral Blood Progenitor Cells Versus Anthracycline and Cyclophosphamide x 4 Followed by Cyclophosphamide, Methotrexate, and 5-fluorouracil x 3 as Adjuvant Treatment for High Risk Operable Stage ii and Stage Iii Breast Cancer in Premenopausal and Young Postmenopausal (Less Than or Equal to 65 Yrs) Patients.
16 Years
65 Years
Female
Breast Cancer
Trial Information
Randomized Trial of High-dose Epirubicin and Cyclophosphamide x 3 Supported by Peripheral Blood Progenitor Cells Versus Anthracycline and Cyclophosphamide x 4 Followed by Cyclophosphamide, Methotrexate, and 5-fluorouracil x 3 as Adjuvant Treatment for High Risk Operable Stage ii and Stage Iii Breast Cancer in Premenopausal and Young Postmenopausal (Less Than or Equal to 65 Yrs) Patients.
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.
Inclusion Criteria
DISEASE CHARACTERISTICS: Histologically proven breast carcinoma in one of the following
categories: 10 or more involved axillary nodes 5 or more involved axillary nodes and
either: Primary tumor estrogen receptor (ER)-negative (less than 10 femtomoles per
milligram of cytosol protein) T3 tumor (regardless of ER status) Total mastectomy or
breast-conserving procedure (lumpectomy or quadrantectomy) required within 6 weeks prior
to randomization Tumor confined to breast and axillary nodes (T1a-c, T2, or T3, N1-2, M0
by the UICC staging system) The following conditions exclude entry: Satellite skin nodules
distant from the primary tumor Supraclavicular node involvement Inoperable, matted
axillary nodes Fixation of primary tumor to chest wall (excluding pectoralis major)
Bilateral breast cancer (any mass in opposite breast unless biopsy-proven benign) Hot
spots on bone scintigram (unless confirmed to be benign) Skeletal pain of unknown cause
Hormone receptor status: ER status determination preferred, but not required
PATIENT CHARACTERISTICS: Age: 16-65 Sex: Women only Menopausal status: Any status
Performance status: ECOG 0-2 Hematopoietic: WBC at least 4,000 Platelets at least 100,000
Hepatic: Bilirubin no greater than 1.1 mg/dL (20 micromoles/L) AST no greater than twice
normal Renal: Creatinine no greater than 1.3 mg/dL (120 micromoles/L) Cardiovascular: Left
ventricular ejection fraction greater than 50% by MUGA Other: No second malignancy except:
Basal cell carcinoma Adequately treated carcinoma in situ of the cervix No significant
nonmalignant disease that would preclude participation No psychiatric or addictive
disorder that would compromise informed consent or participation No pregnant or nursing
women Adequate contraception strongly advised for fertile women
PRIOR CONCURRENT THERAPY: No prior therapy for breast cancer other than surgery (see
Disease Characteristics)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Disease-free survival.
Outcome Description:
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.
Outcome Time Frame:
16 years after randomization.
Safety Issue:
No
Principal Investigator
Russell Basser, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Melbourne Health
Authority:
United States: Federal Government
Study ID:
CDR0000064834
NCT ID:
NCT00002784
Start Date:
June 1996
Completion Date:
December 2011
Related Keywords:
- Breast Cancer
- stage II breast cancer
- stage IIIA breast cancer
- Breast Neoplasms
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