title: Feasibility trial of partial breast irradiation with concurrent dose-dense doxorubicin and cyclophosphamide in early-stage breast cancer.
abstract: OBJECTIVE
  Anthracyclines and concurrent whole-breast irradiation result in prohibitive cutaneous toxicity. We hypothesized that anthracycline-based chemotherapy and concurrent partial breast irradiation (PBI) is safe and conducted a single-arm feasibility trial testing this hypothesis with dose-dense doxorubicin and cyclophosphamide (ddAC).
  
  
  METHODS
  Women with T1-2, N0-1 breast cancer with > or = 3 mm lumpectomy margins received PBI (40.5 Gy, 15 daily 2.7-Gy fractions) concurrently with the first two of four cycles of ddAC (60 and 600 mg/m2 of doxorubicin and cyclophosphamide, respectively, every 14 days with colony-stimulating support). Primary end points were local and systemic toxicity. Additional systemic therapy was given at the physician's discretion.
  
  
  RESULTS
  Twenty-seven patients enrolled between November 2004 and January 2007, but two patients did not receive protocol therapy (one found with additional local disease and one withdrew consent). Twenty-five women completed all planned PBI. Four (16%) of 25 did not complete all ddAC (febrile neutropenia [FN], n = 2; diverticulitis and neutropenia, n = 1; and social/economic reasons, n = 1). Four among the remaining 21 who completed all ddAC had a cycle delayed (FN, n = 1; acute respiratory illness, n = 1; foot blisters, n = 1; perianal dermatitis, n = 1). There was no grade 3 to 4 anemia or thrombocytopenia. Grade 3 nonhematologic toxicities (none grade 4) occurred in 28% (seven of 25) of patients (nausea/vomiting, n = 3; stomatitis, n = 2; contralateral breast abscess, n = 1; fatigue, n = 1; and cough/bronchospasms, n = 1). The observed rate of > or = grade 2 skin toxicity was 0% (0 of 25; one-sided 95% CI, 0% to 11%).
  
  
  CONCLUSIONS
  PBI with concurrent ddAC is feasible, and local/systemic toxicity is acceptable. Larger studies are warranted to assess long-term locoregional control and late toxicities.
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins, 401 N Broadway, Suite 1440, Baltimore, MD 21231, USA. zellari@jhmi.edu
authors.forename: Richard C
authors.initials: RC
authors.lastname: Zellars
authors.forename: Vered
authors.initials: V
authors.lastname: Stearns
authors.forename: Deborah
authors.initials: D
authors.lastname: Frassica
authors.forename: Fariba
authors.initials: F
authors.lastname: Asrari
authors.forename: Theodore
authors.initials: T
authors.lastname: Tsangaris
authors.forename: Lee
authors.initials: L
authors.lastname: Myers
authors.forename: Shirley
authors.initials: S
authors.lastname: DiPasquale
authors.forename: Julie R
authors.initials: JR
authors.lastname: Lange
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Jacobs
authors.forename: Leisha A
authors.initials: LA
authors.lastname: Emens
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Armstrong
authors.forename: John H
authors.initials: JH
authors.lastname: Fetting
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett-Mayer
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff