ANZ 0001 Capecitabine vs CMF in Advanced Breast Cancer

INTERVENTION: ANZ 0001 is an unblinded, multicentre, randomized phase III clinical trial of 465 women with advance disease and not suited to intensive chemotherapy. This study aims to determine whether daily oral chemotherapy with capecitabine is preferable to standard intermittent chemotherapy with CMF in such people. This trial has 3 treatment arms: Intermittent Capecitabine; Continuous Capecitabine; Standard CMF (CMF) ‐ (oral cyclophosphamide days 1‐14; methotrexate and 5‐Fluorouracil both IV days 1 and 8) Intermittent Capecitabine (IC) Intermittent daily oral chemotherapy with capecitabine 2000 mg/m2/day days 1‐14, reviewed and repeated every 3 weeks. The dose of capecitabine is increased to 2500 mg/m2/day if there is no toxicity equal to or greater than grade 1 in cycles 1 and 2. Patients with moderate renal impairment (calculated creatinine clearance of 30 ‐ 50 mL/minute) should not have their dose escalated above 2000 mg/m2 per day. Or Continuous Capecitabine (CC) Continuous daily oral chemotherapy with capecitabine 1300 mg/m2/ day days 1‐21 reviewed and repeated every 3 weeks. There is no dose escalation. CONDITION: Advanced breast cancer PRIMARY OUTCOME: The primary objective is to compare oral chemotherapy with capecitabine to standard intermittent combination chemotherapy with CMF in terms of quality adjusted time to progression SECONDARY OUTCOME: Compliance. Marginal cost‐effectiveness. Overall survival. Patient acceptability and other aspects of health‐related quality of life (HRQL). Safety (side effects). To compare time to progression. Tumour response rates in patients with measurable disease. INCLUSION CRITERIA: Histologic or cytologic diagnosis of breast cancer with at least one of the following: distant metastasis (including just supraclavicular nodes), local invasion of adjacent non‐breast tissue ie T4 or N2 or N3, local recurrence following mastectomy; Treatment with palliative intent, i.e. without realistic hope of cure; Suitable for protocol chemotherapy with either CMF or capecitabine; ECOG performance status of 0 to 3; Neutrophil count greater than or equal to 1.5 x 10 (9)/L and Platelet count greater than or equal to 75 x 10 (9)/L; Creatinine clearance greater than or equal to 30 mL/minute according to the Cockcroft‐Gault Formula; Serum total bilirubin <50 umol/L; Accessible for treatment and follow‐up; Written informed consent; Baseline HRQL forms completed OR the patient cannot read English.