Results of a phase III prospective, randomised trial, comparing mitoxantrone and vinorelbine (MV) in combination with standard FAC/FEC in front-line therapy of metastatic breast cancer

This comparative phase III trial of mitoxantrone + vinorelbine (MV) versus 5-fluorouracil + cyclophosphamide + either doxorubicin or epirubicin (FAC/F EC) in the treatment of metastatic breast cancer was conducted to determine whether MV would produce equivalent efficacy, while resulting in an improv ed tolerance in relation to alopecia and nausea/vomiting. This multicentre study recruited and randomised 281 patients with metastatic breast cancer; 280 were evaluable for response survival and toxicity (138 received FAC/FEC , 142 received MV). Patient characteristics were matched in each arm and st ratification for prior exposure to adjuvant therapy was made prospectively. The overall response rate (ORR) was equivalent in tile two arms (33.3% for FAG, FEC versus 34.5% for MV), but MV was more effective in patients who h ad received prior adjuvant therapy (13% (95% confidence interval (CI) 3-23) for FAC/FEC versus 33% (95% CI 20 47) for MV P = 0.025) with a better prog ression-free survival (PFS) (5 months (range 1-18 months) versus 8 months ( range 1-27 months); P = 0.0007 for FAC/FEC versus MV, respectively) while F AC/ FEC was more: effective in previously untreated patients (ORR 43% (95% CI 33 53) versus 35% (95% CI 25-45), P = 0.26; PFS 9 months (range 0-29 mon ths) versus 6 months (range 0 - 26 months) P = 0.014). Toxicity was monitor ed through the initial six cycles of therapy; febrile neutropenia and delay ed haematological recovery was more frequent for MV (P = 0.001), while naus ea/vomiting of grades 3-4 was greater for FAC/FEC (P = 0.031), as was alope cia (P = 0.0001), cardiotoxicity was the same for the two regimens. MV repr esents a chemotherapy combination with equivalent efficacy to standard FAC/ FEC and improved results for patients who have previously received adjuvant chemotherapy. Toxicity must be balanced to allow for increased haematologi cal suppression and risk of febrile neutropenia with MV compared with a hig her risk of subjectively unpleasant side-effects such as nausea/vomiting an d alopecia with FAC/FEC. (C) 2001 Elsevier Science Ltd. All rights reserved .