combination chemotherapy compared with mitoxantrone in treating older patients with advanced breast cancer

Conditions: Breast Cancer

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. giving drugs in different combinations may kill more tumor cells. purpose: randomized phase ii trial to compare the effectiveness of cyclophosphamide, methotrexate, and fluorouracil with mitoxantrone in treating older patients with recurrent or metastatic breast cancer.

objectives: i. determine the response rate and duration of response of elderly patients with advanced breast cancer treated with first-line chemotherapy with mitigated "classical" cmf (cyclophosphamide/methotrexate/fluorouracil) vs. mitoxantrone (dhad). ii. define the morbidity of cmf and dhad in elderly patients. iii. determine quality of life in these patients. outline: this is a randomized study. patients are stratified by participating institution. the first group receives oral cyclophosphamide on days 1 through 14 and intravenous methotrexate and fluorouracil on days 1 and 8. courses repeat every 4 weeks for a maximum of 6 courses. the second group receives intravenous mitoxantrone every 3 weeks for a maximum of 8 courses. concomitant therapy with hepatotoxic or nephrotoxic drugs (e.g., nsaids) or corticosteroids (even as antiemetics) is not permitted in either group. radiotherapy is allowed provided no more than 50% of the bone marrow is irradiated and at least 1 indicator lesion is unirradiated. patients who complete therapy are followed every 3 months until disease progression. projected accrual: 60 patients will be accrued over approximately 1 year. if extreme differences between arms exist after entry of 30 patients, accrual may be stopped early.

Eligibility criteria:
disease characteristics: histologically proven, progressive, recurrent or metastatic breast cancer in patients over 70 years of age measurable or evaluable disease required, including: lesions of the mediastinum, retroperitoneum, or liver at least 3 cm in diameter on ct scan or ultrasound the following are not considered measurable or evaluable: lymphedema hilar enlargement pleural effusion ascites bone marrow infiltration osteoblastic skeletal lesion no cns metastases hormone receptor status: not specified patient characteristics: age: over 70 sex: not specified menopausal status: postmenopausal performance status: who 0-2 hematopoietic: wbc at least 3,000 platelets at least 100,000 hepatic: bilirubin less than 1.4 mg/dl (25 micromoles/l) renal: creatinine clearance (calculated) greater than 50 ml/min in patients weighing at least 45 kg and measured creatinine clearance at least 50 ml/min in patients weighing less than 45 kg cardiovascular: no congestive heart failure no myocardial infarction within 6 months no severe arrhythmia no complete bundle branch block other: no active uncontrolled infection no mental disorders that may preclude patient follow-up no second malignancy except: adequately treated basal cell carcinoma of the skin adequately treated in situ carcinoma of the cervix prior concurrent therapy: biologic therapy: not specified chemotherapy: no prior chemotherapy for advanced disease at least 1 year since prior adjuvant chemotherapy endocrine therapy: at least 4 weeks since prior estrogens, androgens, and progestins tamoxifen or aminoglutethimide allowed with no waiting period if disease progresses recovery from prior hormonal therapy for metastatic disease required radiotherapy: prior radiotherapy allowed provided: evaluable disease exists outside of treatment field no greater than 50% of bone marrow was irradiated surgery: not specified

Keywords: stage iv breast cancer recurrent breast cancer