title: Phase I/II trial of adjuvant dose-dense docetaxel/epirubicin/cyclophosphamide (TEC) in stage II and III breast cancer.
abstract: 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.
authors.affiliation: Vermont Cancer Center, University of Vermont, Burlington, Vermont 05401, USA. Susan.Burdette-Radoux@vtmednet.org
authors.forename: Susan
authors.initials: S
authors.lastname: Burdette-Radoux
authors.forename: Marie E
authors.initials: ME
authors.lastname: Wood
authors.forename: Julie J
authors.initials: JJ
authors.lastname: Olin
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Laughlin
authors.forename: Abigail M
authors.initials: AM
authors.lastname: Crocker
authors.forename: Takamaru
authors.initials: T
authors.lastname: Ashikaga
authors.forename: Hyman B
authors.initials: HB
authors.lastname: Muss
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007279:Injections, Subcutaneous; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D043823:Taxoids / Q000008:administration & dosage; D013924:Thrombophlebitis / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D015251:Epirubicin; D003520:Cyclophosphamide; D000069585:Filgrastim