Acute hematologic feasibility of G-CSF supported dose-escalated FEC therapy as adjuvant treatment after breast cancer surgery

A study of the feasibility of gradually increased epirubicin and cyclophosp hamide dosage in an FEC regimen with G-CSF (granulocyte colony stimulating factor) support in 18 high-risk breast cancer patients as adjuvant treatmen t was carried out. The FEC regimen was initiated with 5-fluorouracil 600 mg /m(2), epirubicin 75 mg/m(2) and cyclophosphamide 900 mg/m(2) together with G-CSF 5 mu g/kg subcutaneously on days 2-15 q 3 weeks for nine cycles, inc reasing individually through four dose levels to a maximum of 5-FU 600 mg/m (2) (not escalated), epirubicin 120 mg/m(2) and cyclophosphamide 1800 mg/m( 2). Transient cytopenias were regularly observed without major clinical com plications. Rapid recovery and a biphasic overshoot of granulocytes require d individualisation of G-CSF support. During the 6-month treatment period a genial decline in granulocytes, platelets and haemoglobin was observed res ulting in maximal dose intensity in the middle of the treatment period. Com pared to a conventional FEC regimen (5-Fluorouracil 600 mg/m(2), Epirubicin 60 mg/m(2), Cyclophosphamide 600 q 3 w) without dose reductions, it was fe asible to increase the dose of epirubicin by more than 50 per cent with an increased dose intensity between 25 and 70 pet cent. The dose of cyclophosp hamide was increased by more than 100 per cent. All patients suffered from complete alopecia and moderate nausea, bur there was no acute cardiac ol se vere mucosal toxicity. It was concluded that intensified, G-CSF supported F EC therapy can be safely administered in an outpatient setting, provided th e patients are thoroughly informed and adequately monitored. High-risk pati ents are enrolled in a study comparing the described regimen and a myeloabl ative regimen including peripheral stem-cell support. Breast cancel. seems to respond to chemotherapy in a dose dependent manner, suggesting the use o f dose intensified regimens (1,8,9,11). This approach is currently under in vestigation in studies comparing standard regimens with myelo-ablative regi mens in high-risk primary breast cancer (3, 10). In a Scandinavian multicen ter study (2), two high dose regimens, G-CSF supported dose-escalated FEC a nd myeloablative cyclophosphamide-thiotepa-carboplatin with peripheral stem cell support, are compared as adjuvant therapy in operable high-risk breas t cancer. This phase I study was performed to assess the feasibility and ac hievable dose intensity of an individually dose-escalated FEC regimen not i n previous use.