A randomised phase II study of conventional versus accelerated infusional chemotherapy with granulocyte colony-stimulating factor support in advanced breast cancer

Background: Granulocyte colony-stimulating factor (G-CSF) allows cycles of conventional bolus chemotherapy to be accelerated with reduction in treatment time and a boost in dose intensity. Theoretically, this approach could be hazardous with infusional 5-fluorouracil (5-FU) chemotherapy, since G-CSF-stimulated neutrophil proliferation would be occurring in the face of continuous S-phase active 5-FU. We performed this phase IT randomised study to compare the safety, tolerability and efficacy of conventional 3-weekly epirubicin, cyclophosphamide and continuous infusional 5-FU (infusional ECF) to an accelerated 2-weekly schedule with G-CSF support, inpatients with advanced breast cancer. Patients and methods: Twenty-seven patients were randomised, with 14 in the accelerated arm. Patients received bolus epirubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks (conventional arm) or every 2 weeks (accelerated arm) and 5-FU 200 mg/m(2)/day continuous infusion throughout. G-CSF 300 mug/day s.c. on days 10-12 was given each accelerated cycle. Results: There were no treatment delays secondary to inadequate neutrophil or platelet recovery in either arm, with higher median day I neutrophil counts for each cycle in the accelerated arm compared with the conventional arm. Eighty-six per cent of the planned conventional chemotherapy cycles and 82% of the planned accelerated cycles were given. There were no major differences in toxicity between the arms, with the most common grade 3 toxicities being alopecia and stomatitis, Eight patients developed neutropenic sepsis (five in the accelerated arm and three in the conventional arm). Ten patients (77%) responded in the conventional arm and nine (64%) in the accelerated arm. Conclusions: Accelerated infusional ECF with limited G-CSF support is a feasible and well-tolerated regimen with rapid haematological recovery. A 50% increase in relative dose intensity of epirubicin and cyclophosphamide is achieved, while overall treatment time is reduced by 33%.