IBCSG 32-05 / BIG 1-05 - Chemotherapy Adjuvant Study for women at advanced age

INTERVENTION: IBCSG 32‐05 / BIG 1‐05 (CASA) is coordinated by the International Breast Cancer Study Group (IBCSG). The trial will be conducted in Australia and New Zealand by the ANZ Breast Cancer Trials Group. The overall aim of the CASA study is to investigate the role of PLD as adjuvant chemotherapy for older postmenopausal women for whom chemotherapy is indicated, but standard regimens, derived from trials in younger women, are assumed to be too toxic or inconvenient. Some investigators are likely to choose no adjuvant cytotoxic therapy as a standard for frail patients at advanced age, while others will prefer to offer SOME treatment for all patients with endocrine nonresponsive disease. In order to take into consideration both attitudes towards the same problem, the IBCSG has designed two individual complementary randomized options in order to investigate the role of adjuvant cytotoxic chemotherapy for postmenopausal women at advanced age with endocrine nonresponsive early breast cancer. Option 1 (designed for patients who, according to the treating physician and/or to the patient's preferences, are candidates to receive no adjuvant therapy): a. PLD b. No treatment Option 2 (designed for patients who, according to the treating physician and/or to the patient's preferences, should receive some adjuvant treatment): a. PLD b. low dose metronomic cyclophosphamide and methotrexate (CM) Note: Caelyx® (Doxil®), a PLD, is the experimental treatment. PLD (Caelyx, Doxil) is administered intravenously at a dose of 20mg/m2 every 2 weeks for 16 weeks (total of 8 doses). Low‐dose, metronomic cyclophosphamide and methotrexate (CM) is administered for 16 weeks. C = cyclophosphamide 50 mg/day orally continuously for 16 weeks; M = methotrexate 2.5 mg/twice a day orally days 1 and 4 of every week for 16 weeks. CONDITION: Breast Cancer PRIMARY OUTCOME: Breast cancer free interval (BCFI) ‐ BCFI is defined as the time from randomisation to local (including recurrence restricted to the breast after breast conserving treatment), regional, or distant relapse, or contralateral breast cancer. In calculating BCFI, second (non breast) malignancies are ignored and deaths without cancer event are censored at teh time of death. Appearance of ductal carcinoma in‐situ (DCIS) or lobular carcinoma in‐situ (LCIS) either in the ipsilateral or in the contralateral breast is not considered a BCFI event. SECONDARY OUTCOME: Adverse events Competing causes of death. Disease‐free survival (includes second malignancies and deaths) Overall survival Quality of life Second (non‐breast) malignancy Sites of failure Tolerability (percent of patients treated according to the protocol and completing the adjuvant program and percent protocol treatment received) INCLUSION CRITERIA: Histologically proven, hormone receptor negative, completely resected breast cancer confined to the breast and axillary nodes without detected metastases elsewhere; patients must not be candidates for endocrine therapy or standard chemotherapy regimen; margins must be negative for invasive breast cancer and DCIS; adequate bone marrow, renal, and hepatic function; adequate cardiovascular function and geographically accessible for follow‐up.