High-dose sequential epirubicin and cyclophosphamide with peripheral bloodstem cell support for advanced breast cancer: results of a phase II study

The aim of this study was to evaluate the feasibility of a high-dose intens ity and high-dose density multicycle epirubicin and cyclophosphamide regime n with peripheral blood stem cells (PBSC) and haematopoietic growth factor (G-CSF) support in advanced breast cancer patients. From August 1994 to Sep tember 1999, 56 breast cancer patients (8 stage IIIB and 48 stage IV) recei ved 205 courses of cyclophosphamide 3 g m(-2) and epirubicin 100 mg m(-2) e very 14 days. G-CSF 5 mug kg(-1) day(-1) was administered from day 3 to neu trophil recovery. 4 courses were planned. PBSC were collected after course 1, and reinfused after courses 3 and 4, with greater than or equal to 2 x 1 0(6) CD34+ PBSC kg(-1) required for each reinfusion. 48 patients (86%) rece ived all 4 planned courses, Early withdrawal was consecutive to infectious complications (n = 4), severe asthenia (n = 3), haemorrhagic cystitis (n = 1). A median number of 10.8 x 10(6) CD34+ PBSC kg(-1) (range, 3-80) was har vested with 1 or 2 apheresis in 48 patients (94%). Median relative dose int ensity was 91.3% (range, 72-102%). Grade 4 neutrophil toxicity was observed in 100% of patients. Febrile neutropenia was observed in 40% of courses (m edian duration 2 days). Red blood cells and platelets had to be transfused in 54% and 27% of courses, respectively. There were no toxic deaths. Object ive response rate was 69% in stage IV patients (31/45 evaluable, pts), with a 16% complete response rate. Their median progression-free and overall su rvivals were 22.5 and 37 months, respectively. This epirubicine-containing high-dose regimen appeared feasible, albeit with high toxicity. Time-relate d progression parameters exceed commonly reported ones. Controlled studies of upfront sequential high-dose chemotherapy are still needed to evaluate i ts real benefit. (C) 2001 Cancer Research Campaign