Feasibility trial of partial breast irradiation with concurrent dose-dense doxorubicin and cyclophosphamide in early-stage breast cancer

Richard C. Zellars, Vered Stearns, Deborah Frassica, Fariba Asrari, Theodore Tsangaris, Lee Myers, Shirley DiPasquale, Julie R Lange, Lisa Jacobs, Leisha A. Emens, Deborah Kay Armstrong, John H Fetting, Elizabeth Garrett-Mayer, Nancy E. Davidson, Antonio C Wolff

Research output: Contribution to journalArticle

Abstract

Purpose: 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). Patients and Methods: Women with T1-2, N0-1 breast cancer with ≥ 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 ≥ grade 2 skin toxicity was 0% (0 of 25; one-sided 95% CI, 0% to 11%). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)2816-2822
Number of pages7
JournalJournal of Clinical Oncology
Volume27
Issue number17
DOIs
StatePublished - Jun 10 2009
Externally publishedYes

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Doxorubicin
Cyclophosphamide
Breast
Breast Neoplasms
Febrile Neutropenia
Anthracyclines
Bronchial Spasm
Diverticulitis
Skin
Stomatitis
Segmental Mastectomy
Dermatitis
Blister
Neutropenia
Cough
Thrombocytopenia
Abscess
Nausea
Vomiting
Fatigue

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Feasibility trial of partial breast irradiation with concurrent dose-dense doxorubicin and cyclophosphamide in early-stage breast cancer. / Zellars, Richard C.; Stearns, Vered; Frassica, Deborah; Asrari, Fariba; Tsangaris, Theodore; Myers, Lee; DiPasquale, Shirley; Lange, Julie R; Jacobs, Lisa; Emens, Leisha A.; Armstrong, Deborah Kay; Fetting, John H; Garrett-Mayer, Elizabeth; Davidson, Nancy E.; Wolff, Antonio C.

In: Journal of Clinical Oncology, Vol. 27, No. 17, 10.06.2009, p. 2816-2822.

Research output: Contribution to journalArticle

Zellars, Richard C. ; Stearns, Vered ; Frassica, Deborah ; Asrari, Fariba ; Tsangaris, Theodore ; Myers, Lee ; DiPasquale, Shirley ; Lange, Julie R ; Jacobs, Lisa ; Emens, Leisha A. ; Armstrong, Deborah Kay ; Fetting, John H ; Garrett-Mayer, Elizabeth ; Davidson, Nancy E. ; Wolff, Antonio C. / Feasibility trial of partial breast irradiation with concurrent dose-dense doxorubicin and cyclophosphamide in early-stage breast cancer. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 17. pp. 2816-2822.
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title = "Feasibility trial of partial breast irradiation with concurrent dose-dense doxorubicin and cyclophosphamide in early-stage breast cancer",
abstract = "Purpose: 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). Patients and Methods: Women with T1-2, N0-1 breast cancer with ≥ 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 ≥ grade 2 skin toxicity was 0{\%} (0 of 25; one-sided 95{\%} CI, 0{\%} to 11{\%}). Conclusion: 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.",
author = "Zellars, {Richard C.} and Vered Stearns and Deborah Frassica and Fariba Asrari and Theodore Tsangaris and Lee Myers and Shirley DiPasquale and Lange, {Julie R} and Lisa Jacobs and Emens, {Leisha A.} and Armstrong, {Deborah Kay} and Fetting, {John H} and Elizabeth Garrett-Mayer and Davidson, {Nancy E.} and Wolff, {Antonio C}",
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T1 - Feasibility trial of partial breast irradiation with concurrent dose-dense doxorubicin and cyclophosphamide in early-stage breast cancer

AU - Zellars, Richard C.

AU - Stearns, Vered

AU - Frassica, Deborah

AU - Asrari, Fariba

AU - Tsangaris, Theodore

AU - Myers, Lee

AU - DiPasquale, Shirley

AU - Lange, Julie R

AU - Jacobs, Lisa

AU - Emens, Leisha A.

AU - Armstrong, Deborah Kay

AU - Fetting, John H

AU - Garrett-Mayer, Elizabeth

AU - Davidson, Nancy E.

AU - Wolff, Antonio C

PY - 2009/6/10

Y1 - 2009/6/10

N2 - Purpose: 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). Patients and Methods: Women with T1-2, N0-1 breast cancer with ≥ 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 ≥ grade 2 skin toxicity was 0% (0 of 25; one-sided 95% CI, 0% to 11%). Conclusion: 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.

AB - Purpose: 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). Patients and Methods: Women with T1-2, N0-1 breast cancer with ≥ 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 ≥ grade 2 skin toxicity was 0% (0 of 25; one-sided 95% CI, 0% to 11%). Conclusion: 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.

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