Doxorubicin versus methotrexate both combined with cyclophosphamide, 5-fluorouracil and tamoxifen in postmenopausal patients with advanced breast cancer - a randomised study with more than 10 years follow-up from the Danish Breast Cancer Cooperative Group

To evaluate the substitution of methotrexate with doxorubicin (Dox) in CMF- (cyclophosphamide, methotrexate, 5-fluorouracil) containing regimen for adv anced breast cancer, 415 postmenopausal patients below the age of 66 years, naive to chemotherapy, were accrued from 1980 to 1984 and followed-up unti l 1995. They received tamoxifen 30 mg daily orally and by randomisation eit her 400 mg/m(2), cyclophosphamide, 25 mg/m(2) doxorubicin and 500 mg/m(2) 5 -fluorouracil (CAF) or 40 mg/m(2) methotrexate instead of Dox (CMF) intrave nously (i.v.) days 1+8 repeated every 4 weeks. Dox was substituted by metho trexate at a cumulative dose of 550 mg/m(2). Among 341 eligible patients th e response rate and median time to progression was significantly in favour of CAF: 53% CAF versus 36% CMF (P = 0.002) and 11.8 months CAF versus 6.5 m onths CMF (P = 0.001). Median duration of response was 19.5 CAF versus 18.0 CMF months, and survival 20.8 CAF versus 17.4 CMF months (non-significant) . The two regimens were equimyelotoxic. There were no treatment-related fat alities but 1 patient with congestive heart failure on CAF was reported. Na usea/vomiting, stomatitis and infections were modest in both groups, whilst alopecia was more common with CAF. Regression analysis showed that long re currence free interval, good performance status, and no visceral involvemen t was significantly related to long-term survival, whilst the treatment reg imen was not. It is concluded that in chemotherapy-naive patients with adva nced breast cancer Dox-containing regimens are superior and remain the firs t choice of chemotherapy, especially in patients with visceral metastases, until newer drugs and combinations have been proven to be superior. (C) 199 9 Elsevier Science Ltd. All rights reserved.