Annals of Oncology 13:889-894, 2002
© 2002 European Society for Medical Oncology
Original Paper |
A randomised phase II study of conventional versus accelerated infusional chemotherapy with granulocyte colony-stimulating factor support in advanced breast cancer
1The Royal Marsden NHS Trust, London; 2Guys and St Thomas’s NHS Trust, London, UK
Received 26 March 2001; revised 10 December 2001; accepted 9 January 2002.
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 II 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, in patients with advanced breast cancer.
Patients and methods
Twenty-seven patients were randomised, with 14 in the accelerated arm. Patients received bolus epirubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks (conventional arm) or every 2 weeks (accelerated arm) and 5-FU 200 mg/m2/day continuous infusion throughout. G-CSF 300 µg/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 1 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%.
Key words: accelerated, breast cancer, cyclophosphamide, epirubicin, 5-fluorouracil, granulocyte colony-stimulating factor