title: 5-year results of dose-intensive sequential adjuvant chemotherapy for women with high-risk node-positive breast cancer: A phase II study.
abstract: OBJECTIVE
  We conducted a phase II pilot study of dose-intensive adjuvant chemotherapy with doxorubicin followed sequentially by high-dose cyclophosphamide to determine the safety and feasibility of this dose-dense treatment and to estimate the disease-free and overall survival in breast cancer patients with four or more involved axillary lymph nodes.
  
  
  METHODS
  Seventy-three patients received adjuvant treatment with four cycles of doxorubicin 75 mg/m(2) as an intravenous bolus every 21 days, followed by three cycles of cyclophosphamide 3,000 mg/m(2) every 14 days with granulocyte colony-stimulating factor support.
  
  
  RESULTS
  Seventy-one patients were assessable, and all but two completed all planned chemotherapy. There was no treatment-related mortality. The most common toxicity was neutropenic fever, which occurred in 39% of patients. Median disease-free survival is 66 months (95% confidence interval, 34 to 98 months), and median overall survival has not yet been reached. At 5 years of follow-up, the disease-free survival is 51.7%, and overall survival is 60.0%. There is no long-term treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed.
  
  
  CONCLUSIONS
  Our pilot study of doxorubicin followed by cyclophosphamide demonstrates the safety and feasibility of the sequential dose-dense plan. Long-term follow-up, although noncomparative, is promising. However, this regimen is associated with a higher incidence of toxicity (and also higher costs) than the standard dose and schedule of doxorubicin and cyclophosphamide, and therefore it should not be used as conventional therapy in the absence of demonstrated improvement of outcome. Randomized trials testing the dose-dense approach have been completed but not yet reported. Because the sequential plan can decrease overlapping toxicities, it is an appropriate platform for the addition of newer active agents, such as taxanes or monoclonal antibodies.
authors.affiliation: Breast Cancer Medicine Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. hudisc@mskcc.org
authors.forename: C
authors.initials: C
authors.lastname: Hudis
authors.forename: M
authors.initials: M
authors.lastname: Fornier
authors.forename: L
authors.initials: L
authors.lastname: Riccio
authors.forename: D
authors.initials: D
authors.lastname: Lebwohl
authors.forename: J
authors.initials: J
authors.lastname: Crown
authors.forename: T
authors.initials: T
authors.lastname: Gilewski
authors.forename: A
authors.initials: A
authors.lastname: Surbone
authors.forename: V
authors.initials: V
authors.lastname: Currie
authors.forename: A
authors.initials: A
authors.lastname: Seidman
authors.forename: B
authors.initials: B
authors.lastname: Reichman
authors.forename: M
authors.initials: M
authors.lastname: Moynahan
authors.forename: G
authors.initials: G
authors.lastname: Raptis
authors.forename: N
authors.initials: N
authors.lastname: Sklarin
authors.forename: M
authors.initials: M
authors.lastname: Theodoulou
authors.forename: L
authors.initials: L
authors.lastname: Weiselberg
authors.forename: R
authors.initials: R
authors.lastname: Salvaggio
authors.forename: K S
authors.initials: KS
authors.lastname: Panageas
authors.forename: T J
authors.initials: TJ
authors.lastname: Yao
authors.forename: L
authors.initials: L
authors.lastname: Norton
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010865:Pilot Projects; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D004317:Doxorubicin; D003520:Cyclophosphamide