A phase ii pilot trial incorporating bevacizumab into dose-dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node positive breast cancer

A trial coordinated by the Eastern Cooperative Oncology Group

Kathy Miller, A. O'neill, E. A. Perez, A. D. Seidman, G. W. Sledge

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: E2104 was designed to evaluate the safety of two different strategies incorporating bevacizumab into anthracycline-containing adjuvant therapy as a precursor to a definitive randomized phase III trial. Patients and methods: Patients were sequentially assigned to one of two treatment arms. In addition to dose-dense doxorubicin and cyclophosphamide followed by paclitaxel (Taxol) (ddAC→T), all patients received bevacizumab (10 mg/kg every 2 weeks × 26) initiated either concurrently with AC (Arm A: ddBAC→BT→B) or with paclitaxel (Arm B: ddAC→BT→B). The primary end point was incidence of clinically apparent cardiac dysfunction (CHF). Results: Patients enrolled were 226 in number (Arm A 104, Arm B 122). Grade 3 hypertension, thrombosis, proteinuria and hemorrhage were reported for 12, 2, 2 and <1% of patients, respectively. Two patients developed grade 3 or more cerebrovascular ischemia. Three patients in each arm developed CHF. There was no significant difference between arms in the proportion of patients with an absolute decrease in left ventricular ejection fraction of >15% or >10% to below the lower limit of normal post AC or post bevacizumab. Conclusions: Incorporation of bevacizumab into anthracycline-containing adjuvant therapy does not result in prohibitive cardiac toxicity. The definitive phase III trial (E5103) was activated with systematic and extensive cardiac monitoring to define the true impact of bevacizumab on cardiac function.

Original languageEnglish
Pages (from-to)331-337
Number of pages7
JournalAnnals of Oncology
Volume23
Issue number2
DOIs
StatePublished - Feb 2012

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Paclitaxel
Doxorubicin
Cyclophosphamide
Lymph Nodes
Breast Neoplasms
Anthracyclines
Proteinuria
Thrombosis
Therapeutics
Bevacizumab
Hemorrhage
Hypertension
Safety
Incidence

Keywords

  • Angiogenesis
  • Breast cancer
  • Cardiomyopathy
  • Clinical trial
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

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title = "A phase ii pilot trial incorporating bevacizumab into dose-dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node positive breast cancer: A trial coordinated by the Eastern Cooperative Oncology Group",
abstract = "Background: E2104 was designed to evaluate the safety of two different strategies incorporating bevacizumab into anthracycline-containing adjuvant therapy as a precursor to a definitive randomized phase III trial. Patients and methods: Patients were sequentially assigned to one of two treatment arms. In addition to dose-dense doxorubicin and cyclophosphamide followed by paclitaxel (Taxol) (ddAC→T), all patients received bevacizumab (10 mg/kg every 2 weeks × 26) initiated either concurrently with AC (Arm A: ddBAC→BT→B) or with paclitaxel (Arm B: ddAC→BT→B). The primary end point was incidence of clinically apparent cardiac dysfunction (CHF). Results: Patients enrolled were 226 in number (Arm A 104, Arm B 122). Grade 3 hypertension, thrombosis, proteinuria and hemorrhage were reported for 12, 2, 2 and <1{\%} of patients, respectively. Two patients developed grade 3 or more cerebrovascular ischemia. Three patients in each arm developed CHF. There was no significant difference between arms in the proportion of patients with an absolute decrease in left ventricular ejection fraction of >15{\%} or >10{\%} to below the lower limit of normal post AC or post bevacizumab. Conclusions: Incorporation of bevacizumab into anthracycline-containing adjuvant therapy does not result in prohibitive cardiac toxicity. The definitive phase III trial (E5103) was activated with systematic and extensive cardiac monitoring to define the true impact of bevacizumab on cardiac function.",
keywords = "Angiogenesis, Breast cancer, Cardiomyopathy, Clinical trial, Vascular endothelial growth factor",
author = "Kathy Miller and A. O'neill and Perez, {E. A.} and Seidman, {A. D.} and Sledge, {G. W.}",
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T1 - A phase ii pilot trial incorporating bevacizumab into dose-dense doxorubicin and cyclophosphamide followed by paclitaxel in patients with lymph node positive breast cancer

T2 - A trial coordinated by the Eastern Cooperative Oncology Group

AU - Miller, Kathy

AU - O'neill, A.

AU - Perez, E. A.

AU - Seidman, A. D.

AU - Sledge, G. W.

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N2 - Background: E2104 was designed to evaluate the safety of two different strategies incorporating bevacizumab into anthracycline-containing adjuvant therapy as a precursor to a definitive randomized phase III trial. Patients and methods: Patients were sequentially assigned to one of two treatment arms. In addition to dose-dense doxorubicin and cyclophosphamide followed by paclitaxel (Taxol) (ddAC→T), all patients received bevacizumab (10 mg/kg every 2 weeks × 26) initiated either concurrently with AC (Arm A: ddBAC→BT→B) or with paclitaxel (Arm B: ddAC→BT→B). The primary end point was incidence of clinically apparent cardiac dysfunction (CHF). Results: Patients enrolled were 226 in number (Arm A 104, Arm B 122). Grade 3 hypertension, thrombosis, proteinuria and hemorrhage were reported for 12, 2, 2 and <1% of patients, respectively. Two patients developed grade 3 or more cerebrovascular ischemia. Three patients in each arm developed CHF. There was no significant difference between arms in the proportion of patients with an absolute decrease in left ventricular ejection fraction of >15% or >10% to below the lower limit of normal post AC or post bevacizumab. Conclusions: Incorporation of bevacizumab into anthracycline-containing adjuvant therapy does not result in prohibitive cardiac toxicity. The definitive phase III trial (E5103) was activated with systematic and extensive cardiac monitoring to define the true impact of bevacizumab on cardiac function.

AB - Background: E2104 was designed to evaluate the safety of two different strategies incorporating bevacizumab into anthracycline-containing adjuvant therapy as a precursor to a definitive randomized phase III trial. Patients and methods: Patients were sequentially assigned to one of two treatment arms. In addition to dose-dense doxorubicin and cyclophosphamide followed by paclitaxel (Taxol) (ddAC→T), all patients received bevacizumab (10 mg/kg every 2 weeks × 26) initiated either concurrently with AC (Arm A: ddBAC→BT→B) or with paclitaxel (Arm B: ddAC→BT→B). The primary end point was incidence of clinically apparent cardiac dysfunction (CHF). Results: Patients enrolled were 226 in number (Arm A 104, Arm B 122). Grade 3 hypertension, thrombosis, proteinuria and hemorrhage were reported for 12, 2, 2 and <1% of patients, respectively. Two patients developed grade 3 or more cerebrovascular ischemia. Three patients in each arm developed CHF. There was no significant difference between arms in the proportion of patients with an absolute decrease in left ventricular ejection fraction of >15% or >10% to below the lower limit of normal post AC or post bevacizumab. Conclusions: Incorporation of bevacizumab into anthracycline-containing adjuvant therapy does not result in prohibitive cardiac toxicity. The definitive phase III trial (E5103) was activated with systematic and extensive cardiac monitoring to define the true impact of bevacizumab on cardiac function.

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