None listed
Conditions
Brief summary
This clinical trial is for premenopausal women who after their breast cancer surgery are found to have breast cancer which is not suitable for hormonal treatment alone, 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 for breast cancer. The optimal chemotherapy program involves two short courses of different chemotherapy programmes (AC [doxorubicin or epirubicin + cyclophosphamide] & CMF [cyclophosphamide, methotrexate, 5-fluorouracil). 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, as well as whether she will have Tamoxifen or not will be allocated by a process called randomisation which is similar to tossing a coin. This trial will test whether the delay between the chemotherapy courses is needed as well as if there is an extra benefit of adding a hormonal treatment to the chemotherapy.
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)
Arm B: cycles of Doxorubicin (60mg/m^2 iv) or Epirubicin (90mg/m^2 iv) and cyclophosphamide (600mg/m^2 iv) ond day 1 of a 21 day cycle, followed by a 16 week gap pr
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) Arm B: cycles of Doxorubicin (60mg/m^2 iv) or Epirubicin (90mg/m^2 iv) and cyclophosphamide (600mg/m^2 iv) ond 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) Arm C: 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 iv administer 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 (20mg orally daily) for up to 5 years from randomisation. Arm D: 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 (20mg 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 No maximum
Healthy volunteers
No
Inclusion criteria
• Premenopausal women (aged 18 or over) 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 of inflammatory breast cancer, or with distant metastases.• Bilateral malignancies, or mass in opposite breast, unless mass has been proven by biopsy to be benign• Patients in whom margins of resected specimen contained tumour cells• Previous or concomitant other malignancy except basal or squamous cell carcinoma of skin or in situ carcinoma of cervix• Prior therapy for breast cancer including prior radiation, chemotherapy or endocrine therapy• Non-malignant systemic diseases preventing treatment options or follow-up• Psychiatric or addictive disorders preventing informed consent• Bone scan showing hot spots which cannot be confirmed as benign disease• Pregnant or lactating women
Outcome results
None listed