None listed
Conditions
Brief summary
This clinical trial is for post and perimenopausal women who after their breast cancer surgery are found to have breast cancer which does not contain hormone receptors (is not stimulated by hormones), and who also have cancer cells in the glands of the arm pit (‘positive axillary lymph nodes’). It is known that these women will benefit substantially by having chemotherapy after surgery as well as long term hormonal treatment for their breast cancer. The optimal chemotherapy program involves two short courses of different chemotherapy programmes (AC & CMF). It is not known whether the second chemotherapy course (CMF) should begin immediately after the first course (AC) or whether it should be delayed (with a break in between). Whether or not a patient will have a gap between her chemotherapy programmes will be allocated by a process called randomisation which is similar to tossing a coin. This clinical trial will assess which method of giving chemotherapy is optimal for decreasing the chance of breast cancer recurrence and increasing patient survival.
Interventions
Arm A: 4 cycles of Doxorubicin (60mg/m^2 iv) or Epirubicin (90mg/m^2 iv) and cyclophosphamide (600mg/m^2 iv) on day 1 of a 21 day cycle, followed by 3 cycles (1 cycle = 28 days) of Cyclophosphamide (100 mg/m^2 orally administered on Days 1-14), Methotrexate (40mg/m^2 iv on days 1 & 8) and 5-fluorouracil (600mg/m^2 iv on days 1 & 8) followed by treatment with Tamoxifen (orally 20mg daily) for up to 5 years from randomisation.
Arm B: 4 cycles of Doxorubicin (60mg/m^2 iv) or Epirubicin (90mg/m^2 i
Arm A: 4 cycles of Doxorubicin (60mg/m^2 iv) or Epirubicin (90mg/m^2 iv) and cyclophosphamide (600mg/m^2 iv) on day 1 of a 21 day cycle, followed by 3 cycles (1 cycle = 28 days) of Cyclophosphamide (100 mg/m^2 orally administered on Days 1-14), Methotrexate (40mg/m^2 iv on days 1 & 8) and 5-fluorouracil (600mg/m^2 iv on days 1 & 8) followed by treatment with Tamoxifen (orally 20mg daily) for up to 5 years from randomisation. Arm B: 4 cycles of Doxorubicin (60mg/m^2 iv) or Epirubicin (90mg/m^2 iv) and cyclophosphamide (600mg/m^2 iv) on day 1 of a 21 day cycle, followed by a 16 week gap prior to commencing 3 cycles (1 cycle = 28 days) of Cyclophosphamide (100 mg/m^2 orally administered on Days 1-14), Methotrexate (40mg/m^2 iv on days 1 & 8) and 5-fluorouracil (600mg/m^2 iv on days 1 & 8). Followed by treatment with Tamoxifen (orally 20mg daily) for up to 5 years from randomisation Arm C: 4 cycles of Doxorubicin (60mg/m^2 iv) or Epirubicin (90mg/m^2 iv) and cyclophosphamide (600mg/m^2 iv) on day 1 of a 21 day cycle, followed by 3 cycles (1 cycle = 28 days) of Cyclophosphamide (100 mg/m^2 orally administered on Days 1-14), Methotrexate (40mg/m^2 iv on days 1 & 8) and 5-fluorouracil (600mg/m^2 iv on days 1 & 8) Followed by treatment with Toremifene (60mg orally daily) for up to 5 years from randomisation. Arm D: 4 cycles of Doxorubicin (60mg/m^2 iv) or Epirubicin (90mg/m^2 iv) and cyclophosphamide (600mg/m^2 iv) on day 1 of a 21 day cycle, followed by a 16 week gap prior to commencing 3 cycles (1 cycle = 28 days) of Cyclophosphamide (100 mg/m^2 orally administered on Days 1-14), Methotrexate (40mg/m^2 iv on days 1 & 8) and 5-fluorouracil (600mg/m^2 iv on days 1 & 8). Followed by treatment with Toremifene (60mg orally daily) for up to 5 years from randomisation
Sponsors
International Breast Cancer Study Group
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
• Post/perimenopausal women with histologically proven primary breast cancer• Positive lymph nodes (metastases detected in one or more of at least 8 ipsilateral axillary nodes examined). Primary tumour must be classified as T1a,b,c ,T2 or T3, pN1, M0.• Patients must be judged not suitable for treatment with endocrine therapy alone. Estrogen receptor status must be known before randomisation• Patients must have had:a) Either total mastectomy or breast conserving procedureb) Axillary clearance with at least 8 lymph nodes available for pathological examinationc) Primary breast cancer surgical procedure must be within 6 weeks prior to randomisation• Tumour must be confined to breast without detected metastases other than those within lymph nodes• Adequate marrow function (WBC > 4.0 x 10^9/l and platelet count > 100 x 10^9/l)• Adequate renal function (serum creatinine < 120umol/l) and hepatic function (serum bilirubin < 20 umol/l, AST (SGOT) < 60 i.u./l)• Informed consent• Geographically accessible for follow-up
Exclusion criteria
• Patients without axillary node involvement• Malignant tumours other than carcinoma• T4 carcinoma with ulceration of skin, infiltration of skin, peau d'orange or inflammatory breast cancer or with distant metastases• Bilateral malignancies, or with mass in opposite breast• Patients in whom the margins of the resected specimen contained tumour cells• Previous or concomitant other malignancy except basal or squamous cell carcinoma of skin or adequately treated in situ carcinoma of cervix• Patients who have received prior therapy for breast cancer including irradiation, chemotherapy or endocrine therapy• Patients with non-malignant systemic diseases preventing them from undergoing any of the treatment options or prolonged follow-up• Patients with psychiatric or addictive disorders preventing them from giving them informed consent• Bone scan showing hot spots which cannot be confirmed as benign disease
Outcome results
None listed