title: Increased dose density is feasible: a pilot study of adjuvant epirubicin and cyclophosphamide followed by paclitaxel, at 10- or 11-day intervals with filgrastim support in women with breast cancer.
abstract: OBJECTIVE
  Because Cancer and Leukemia Group B 9741 trial showed a benefit for every 14-day administration of chemotherapy compared with every 21-day treatment, we hypothesized that even greater dose density would be more effective. We conducted a pilot trial to assess the feasibility of dose-dense chemotherapy consisting of a standard regime at 10- to 11-day intervals in the adjuvant/neoadjuvant setting. A 2-day window was allowed for scheduling logistics.
  
  
  METHODS
  Thirty-nine women with early-stage breast carcinoma were accrued from April 2004 to October 2004. Median age was 47 years (range, 26-67 years). Patients received therapy with 100 mg/m(2) epirubicin and 600 mg/m(2) cyclophosphamide (EC) q 10 to 11 days for four cycles followed by 175 mg/m(2) paclitaxel q 10 to 11 days for four cycles, all with filgrastim support (300 microg s.c. daily) from day 2 to 24 h before the next treatment.
  
  
  RESULTS
  Thirty-five (90%) patients completed all planned therapy. The median intertreatment interval was 10 days (range, 8-28 days). Cycles (80.7%) were delivered at no more than 10- to 11-day intervals. There were five dose reductions of 25% for grade 3 nonhematologic toxicity in five patients. Six (16%) patients developed febrile neutropenia defined as temperature >38 degrees C with absolute neutrophil count <1,000/microL. All febrile neutropenia was during therapy with EC. Other grade 3 toxicities included bone pain, hand and foot syndrome, neuropathy, mucositis, nausea, and vomiting.
  
  
  CONCLUSIONS
  Therapy with EC for four cycles followed by paclitaxel for four cycles at 10- to 11-day intervals is feasible. The approximately 30% reduction in intertreatment interval compared with every 14-day treatment could increase the efficacy of adjuvant chemotherapy.
authors.affiliation: Breast Cancer Medicine Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. fornierm@mskcc.org
authors.forename: Monica N
authors.initials: MN
authors.lastname: Fornier
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Seidman
authors.forename: Diana
authors.initials: D
authors.lastname: Lake
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Andrea
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Bromberg
authors.forename: Mark
authors.initials: M
authors.lastname: Robson
authors.forename: Catherine
authors.initials: C
authors.lastname: Van Poznak
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Panageas
authors.forename: Marietta
authors.initials: M
authors.lastname: Atienza
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D015251:Epirubicin / Q000008:administration & dosage*; D005240:Feasibility Studies; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D010865:Pilot Projects; D011994:Recombinant Proteins; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D000069585:Filgrastim