Feasibility trial of partial breast irradiation with concurrent dose-dense doxorubicin and cyclophosphamide in early-stage breast cancer.
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.
Zellars
Richard C
RC
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins, 401 N Broadway, Suite 1440, Baltimore, MD 21231, USA. zellari@jhmi.edu
Stearns
Vered
V
Frassica
Deborah
D
Asrari
Fariba
F
Tsangaris
Theodore
T
Myers
Lee
L
DiPasquale
Shirley
S
Lange
Julie R
JR
Jacobs
Lisa K
LK
Emens
Leisha A
LA
Armstrong
Deborah K
DK
Fetting
John H
JH
Garrett-Mayer
Elizabeth
E
Davidson
Nancy E
NE
Wolff
Antonio C
AC