Feasibility of two dose-dense FEC regimens with growth factor support for adjuvant therapy in patients with early breast cancer: results from a randomised study of the Central European Cooperative Oncology Group (CECOG)
Addition of epirubicin to adjuvant chemotherapy can provide important benefits for patients with early breast cancer, but the optimal dose remains unclear. Further improvements can be achieved with dose-dense regimens, but densification of fluorouracil/epirubicin/cyclophosphamide (FEC) has proved difficult, with FEC60 providing little benefit over standard chemotherapy and FEC100 associated with toxicity. We investigated the feasibility of two intermediate dose-dense FEC regimens. Patients were randomised to six cycles of FEC75 or FEC90, with all three drugs given on day 1 of each 14-day cycle. Patients also received pegfilgrastim 6 mg as a single subcutaneous injection on day 2 of each cycle. The primary efficacy endpoint was the proportion of subjects receiving ≥85% relative dose intensity and was achieved by 96% and 88% of patients in the FEC75 and FEC90 arms, respectively. Of 147 FEC75 infusions, 4.1% were delayed, while 9.8% of 143 FEC90 infusions were delayed. The most common reasons for delay were adverse events and personal/logistical reasons. One dose reduction occurred during the study (FEC90), related to diarrhoea. Grade 3–4 haematological toxicities were reported in two patients in the FEC90 arm. There were no incidences of febrile neutropenia during the study. The most common adverse events were increases in liver enzymes and gastrointestinal events; no event resulted in discontinuation. Only one patient (FEC90) experienced serious adverse events (vomiting and throat oedema). In conclusion, dose-dense FEC75 and FEC90 are feasible with pegfilgrastim support. These regimens are associated with a very low risk of Grade 3–4 toxicity.