None listed
Conditions
Brief summary
The prognosis of metastatic and recurrent breast cancer remains poor. Systemic cytotoxic chemotherapy produces objective remission in a majority of cases, but the duration of such remissions is short. Early sequential studies suggested that a plateau may have been reached both in the proportion of patients achieving remission and in remission duration. Questions of interest concern optimal usage of existing agents, with particular reference to maintenance of quality of life during treatment. Experience from earlier protocols have indicated the unpopularity of maintaining high dosage Adriamycin containing combination chemotherapy until progressive disease or until maximum tolerable cumulative Adriamycin dosage. If similar control of disease could be obtained with an intermittent chemotherapy schedule, patients would enjoy periods without the side effects of chemotherapy, presumably to the improvement of their quality of life. This study was therefore designed to compare continuous chemotherapy, administered until disease progression, with intermittent therapy, whereby treatment is stopped after 3 cycles and then repeated for three more cycles only when there was evidence of disease progression.
Interventions
Patients were randomised to receive continuous or intermittent therapy with Adriamycin intra venous (IV) 50 mg/m2 on day 1 plus Cyclophosphamide IV 750 mg/m2 on day 1 (AC) (21 day cycles), or Cyclophosphamide 100 mg/m2 orally day 1-14, Methotrexate 40 mg/m2 IV day 1 & 8, Fluorouracil 600 mg/m2 IV day 1 & 8, and Prednisone 40 mg/m2 orally day 1-14 (CMFP) (28 day cycles). For patients randomised to continuous AC therapy, cycles were repeated until disease progression, or until cumulative Adriamyci
Patients were randomised to receive continuous or intermittent therapy with Adriamycin intra venous (IV) 50 mg/m2 on day 1 plus Cyclophosphamide IV 750 mg/m2 on day 1 (AC) (21 day cycles), or Cyclophosphamide 100 mg/m2 orally day 1-14, Methotrexate 40 mg/m2 IV day 1 & 8, Fluorouracil 600 mg/m2 IV day 1 & 8, and Prednisone 40 mg/m2 orally day 1-14 (CMFP) (28 day cycles). For patients randomised to continuous AC therapy, cycles were repeated until disease progression, or until cumulative Adriamycin dosage of 450 mg/m2, after which the regimen changed to Vincristine 2 mg (total) IV day 1, Methotrexate 50 mg/m2 IV day 1 & 15, and Fluouracil 600 mg/m2 IV day 1 & 15 (VMF) (28 day cycles), given until disease progression or until 18 months after commencement of initial AC chemotherapy, whichever is earlier. Patients randomised to intermittent AC therapy received 3 cycles, those without progressive disease at that time will be observed without chemotherapy until disease progression. They will then receive AC for a maximum of 3 further cycles, if there is further disease progression after 2 cycles the patient will be off study treatment. Patients with complete response, partial response or stable disease after each 3 cycle block of AC will then be observed for a further period without therapy until disease progression, and at that time re-treated with 3 cycles of AC until a cumulative Adriamycin dose of 450 mg/m2 is reached, VMF will be substituted for AC in 3 cycle blocks until progressive disease. For patients randomised to continuous CMFP, cycles will be repeated until disease progression or for 18 months, whichever occurs sooner. Patients randomised to intermittent CMFP will receive 3 cycles, those without progressive disease at that time will be observed without chemotherapy until disease progression. They will then receive further CMFP for 3 cycles, if there is further disease progression after 2 cycles the patient will be off study treatment. Other patients will again be observed without treatment until disease progression and continue to receive blocks of 3 cycles of CMFP at each relapse until disease progression continues despite such therapy.
Sponsors
Ludwig Institute for Cancer Research
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
0 to No maximum
Healthy volunteers
No
Inclusion criteria
Histologically confirmed primary breast cancer with recurrent and/or metastatic disease. No previous cytotoxic chemotherapy for recurrent or metastatic breast cancer. Measurable or evaluable disease. Adequate marrow reserves. Performance status of 3 or better (0-3). Accessible for follow-up. Informed consent. Evidence of adequate renal and hepatic function, unless abnormality due to hepatic metastes.
Exclusion criteria
Past or current malignancies at other sites, except adequately treated squamous or basal cell carcinoma of the skin, or coned biopsied in situ carcinoma of the cervix. Radiotherapy in excess of regional therapy to primary disease, cranial therapy, or limited localised therapy. Past or present congestive cardiac failure, uncontrolled hypertension with left ventricular hypertrophy, left ventricular hypertrophy, or uncorrected left ventricular outflow obstruction. Patients whose only demonstratable malignancy is intracranial. Diabetes mellitus.
Outcome results
None listed