Pilot study of bevacizumab in combination with docetaxel and cyclophosphamide as adjuvant treatment for patients with early stage HER-2 negative breast cancer, including analysis of candidate circulating markers of cardiac toxicity: ICORG 08-10 trial.

bevacizumab breast cancer cardiotoxicity biomarker docetaxel/cyclophosphamide

Journal

Therapeutic advances in medical oncology
ISSN: 1758-8340
Titre abrégé: Ther Adv Med Oncol
Pays: England
ID NLM: 101510808

Informations de publication

Date de publication:
2019
Historique:
received: 14 08 2018
accepted: 29 05 2019
entrez: 7 8 2019
pubmed: 7 8 2019
medline: 7 8 2019
Statut: epublish

Résumé

Combining bevacizumab and chemotherapy produced superior response rates compared with chemotherapy alone in metastatic breast cancer. As bevacizumab may cause hypertension (HTN) and increase the risk of cardiac failure, we performed a pilot study to evaluate the feasibility and toxicity of a non-anthracycline-containing combination of docetaxel with cyclophosphamide and bevacizumab in early stage breast cancer patients. Treatment consisted of four 3-weekly cycles of docetaxel and cyclophosphamide (75/600 mg/m A total of 106 patients were accrued in nine sites. Median follow up was 65 months (1-72 months). Seventeen protocol-defined relapse events were observed, accounting for an overall disease-free survival (DFS) rate of 84%. The DFS rates for hormone receptor positive (HR+) and triple-negative (TN) patients were 95% We observed a low relapse rate in node-positive, HR+ patients; however, results in TN breast cancer were less encouraging. Given the negative results of three large phase III trials, it is unlikely that this approach will be investigated further. ClinicalTrials.gov Identifier: NCT00911716.

Sections du résumé

BACKGROUND BACKGROUND
Combining bevacizumab and chemotherapy produced superior response rates compared with chemotherapy alone in metastatic breast cancer. As bevacizumab may cause hypertension (HTN) and increase the risk of cardiac failure, we performed a pilot study to evaluate the feasibility and toxicity of a non-anthracycline-containing combination of docetaxel with cyclophosphamide and bevacizumab in early stage breast cancer patients.
METHODS METHODS
Treatment consisted of four 3-weekly cycles of docetaxel and cyclophosphamide (75/600 mg/m
RESULTS RESULTS
A total of 106 patients were accrued in nine sites. Median follow up was 65 months (1-72 months). Seventeen protocol-defined relapse events were observed, accounting for an overall disease-free survival (DFS) rate of 84%. The DFS rates for hormone receptor positive (HR+) and triple-negative (TN) patients were 95%
CONCLUSIONS CONCLUSIONS
We observed a low relapse rate in node-positive, HR+ patients; however, results in TN breast cancer were less encouraging. Given the negative results of three large phase III trials, it is unlikely that this approach will be investigated further.
TRIAL REGISTRATION BACKGROUND
ClinicalTrials.gov Identifier: NCT00911716.

Identifiants

pubmed: 31384312
doi: 10.1177/1758835919864236
pii: 10.1177_1758835919864236
pmc: PMC6657121
doi:

Banques de données

ClinicalTrials.gov
['NCT00911716']

Types de publication

Journal Article

Langues

eng

Pagination

1758835919864236

Déclaration de conflit d'intérêts

Conflict of interest statement: The authors declare that there is no conflict of interest.

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Auteurs

Giuseppe Gullo (G)

Cancer Trials Ireland (formerly All-Ireland Clinical Oncology Research Group), Dublin Ireland.

Alex J Eustace (A)

Molecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.

Alexandra Canonici (A)

Molecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.

Denis M Collins (D)

Molecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.

Michael J Kennedy (MJ)

Department of Medical Oncology, St James Hospital, Dublin, Ireland.

Liam Grogan (L)

Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland.

Oscar Breathhnach (O)

Department of Medical Oncology, Beaumont Hospital, Dublin, Ireland.

John McCaffrey (J)

Department of Medical Oncology, Mater Hospital, Dublin, Ireland.

Maccon Keane (M)

Department of Medical Oncology, University Hospital Galway, Galway, Ireland.

Michael J Martin (MJ)

Department of Medical Oncology, Sligo University Hospital, Sligo, Ireland.

Rajnish Gupta (R)

Department of Medical Oncology, University Hospital Limerick, Limerick, Ireland.

Gregory Leonard (G)

Department of Medical Oncology, University Hospital Galway, Galway, Ireland.

Miriam O'Connor (M)

Department of Medical Oncology, University Hospital Waterford, Waterford, Ireland.

Paula M Calvert (PM)

Department of Medical Oncology, University Hospital Waterford, Waterford, Ireland.

Paul Donnellan (P)

Department of Medical Oncology, University Hospital Galway, Galway, Ireland.

Janice Walshe (J)

Department of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland.

Enda McDermott (E)

Department of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland.

Kathleen Scott (K)

Cancer Trials Ireland (formerly All Ireland Co-operative Oncology Research Group), DCU Alpha, Dublin, Ireland.

Andres Hernando (A)

Cancer Trials Ireland (formerly All Ireland Co-operative Oncology Research Group), DCU Alpha, Dublin, Ireland.

Imelda Parker (I)

Cancer Trials Ireland (formerly All Ireland Co-operative Oncology Research Group), DCU Alpha, Dublin, Ireland.

David W Murray (D)

Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.

Alice C O'Farrell (A)

Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.

Ashwini Maratha (A)

Oncomark Ltd, University College Dublin, Dublin, Ireland.

Patrick Dicker (P)

Department of Epidemiology and Public Health Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland.

Mairin Rafferty (M)

Oncomark Ltd, University College Dublin, Dublin, Ireland.

Verena Murphy (V)

Cancer Trials Ireland (formerly All Ireland Co-operative Oncology Research Group), DCU Alpha, Dublin, Ireland.

Norma O'Donovan (N)

Molecular Therapeutics for Cancer in Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.

William M Gallagher (W)

Oncomark Ltd, University College Dublin, Dublin, Ireland.

Bonnie Ky (B)

Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Dimitrios Tryfonopoulos (D)

Department of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland.

Brian Moulton (B)

Clinical Oncology Development Europe, Dublin, Ireland.

Annette T Byrne (A)

Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.

John Crown (J)

Department of Medical Oncology, St Vincent's University Hospital, Dublin, Ireland.

Classifications MeSH