Phase I/II trial of adjuvant dose-dense docetaxel/epirubicin/cyclophosphamide (TEC) in stage II and III breast cancer.

UNLABELLED: This phase I/II trial investigates the safety and feasibility of six cycles of concurrent taxane, anthracycline and cyclophosphamide on a dose dense schedule. Patients with stage II/III breast cancer were treated with docetaxel (T) 75 mg/m(2), epirubicin (E) 75 mg/m(2) (cohort 1, n = 3) or 100 mg/m(2) (cohort 2, n = 12), and cyclophosphamide (C) 500 mg/m(2) IV on day 1, with pegfilgrastim 6 mg subcutaneously on day 2, every 2 weeks for six cycles. Patients were assessed for toxicity every 2 weeks; cardiac function and response (if neoadjuvant) were assessed after six cycles. All patients in cohort 1 received 100% planned dose intensity; in cohort 2, five of twelve patients received 100% and 11/12 received >80%. There were no dose reductions or delays for day 1 myelotoxicity. Dose reductions as a result of febrile neutropenia (FN) occurred in cohort 2, with six of twelve patients experiencing FN in seven of sixty-nine cycles. Six patients had anemia > or =grade 3; five received RBC transfusion and seven received an erythropoietic growth factor. Four patients required dose reductions for nonhematologic toxicity (two mucositis; one neurotoxicity; one diarrhea + cellulitis). Four patients developed thrombophlebitis, which was associated with FN in one of four. Two of fourteen evaluable patients had asymptomatic decreases in LVEF >10%; all remained within normal range. All four patients receiving neoadjuvant TEC had significant clinical responses (one CR, three PR). No pathologic CRs were seen.

CONCLUSIONS: Dose dense TEC chemotherapy is feasible, has acceptable toxicity at doses equivalent to TAC (docetaxel 75 mg/m(2), epirubicin 75 mg/m(2), cyclophosphamide 600 mg/m(2)), and has moderate but manageable toxicity using a higher epirubicin dose of 100 mg/m(2), with FN occurring in six of twelve patients at the higher dose.