Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2019

01-07-2019 | Breast Cancer | Clinical trial

Dose intensity in anthracycline-based chemotherapy for metastatic breast cancer: mature results of the randomised clinical trial ANZ 9311

Authors: Stephen. P. Ackland, V. Gebski, N. Zdenkowski, A. Wilson, M. Green, S. Tees, H. Dhillon, G. Van Hazel, J. Levi, R. J. Simes, J. F. Forbes, A. S. Coates, for Breast Cancer Trials Ltd (formerly known as the Australia and New Zealand Breast Cancer Trials Group)

Published in: Breast Cancer Research and Treatment | Issue 2/2019

Login to get access

Abstract

Purpose

The separate impacts of dose and dose intensity of chemotherapy for metastatic breast cancer remain uncertain. The primary objective of this trial was to compare a short, high-dose, intensive course of epirubicin and cyclophosphamide (EC) with a longer conventional dose regimen delivering the same total dose of chemotherapy.

Methods

This open label trial randomised 235 women with metastatic breast cancer to receive either high-dose epirubicin 150 mg/m2 and cyclophosphamide 1500 mg/m2 with filgrastim support every 3 weeks for 3 cycles (HDEC) or standard dose epirubicin 75 mg/m2 and cyclophosphamide 750 mg/m2 every 3 weeks for 6 cycles (SDEC). Primary outcomes were time to progression, overall survival and quality of life.

Results

In 118 patients allocated HDEC 90% of the planned dose was delivered, compared to 96% in the 117 participants allocated SDEC. There were no significant differences in the time to disease progression (5.7 vs. 5.8 months, P = 0.19) or overall survival (14.5 vs. 16.5 months, P = 0.29) between HDEC and SDEC, respectively. Patients on HDEC reported worse quality of life during therapy, but scores improved after completion to approximate those reported by patients allocated SDEC. Objective tumour response was recorded in 33 (28%) on HDEC and 42 patients (36%) on SDEC. HDEC produced more haematologic toxicity.

Conclusion

For women with metastatic breast cancer, disease progression, survival or quality of life were no better with high-dose intensity compared to standard dose EC chemotherapy.
Australian Clinical Trials Registry registration number ACTRN12605000478617.
Appendix
Available only for authorised users
Literature
1.
International Agency for Research on Cancer (GLOBOCAN 2012) Estimated cancer incidence, prevalence and mortality worldwide in 2012. WHO 2012
2.
Australian Institute of Health and Welfare (2014) Cancer in Australia: an overview. Australian Institute of Health and Welfare & Australasian Association of Cancer Registries, Canberra
3.
Cardoso F, Costa A, Senkus E et al (2017) 3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3). Ann Oncol 28:16–33CrossRefPubMed
4.
Skipper HE (1971) Kinetics of mammary tumor cell growth and implications for therapy. Cancer 28:1479–1499CrossRefPubMed
5.
Hryniuk W, Bush H (1984) The importance of dose intensity in chemotherapy of metastatic breast cancer. J Clin Oncol 2:1281–1288CrossRef
6.
Soley B, Banu A (2012) Dose-dense chemotherapy for breast cancer. Breast J 18:261–266CrossRef
7.
Tannock IF, Boyd NF, DeBoer G et al (1988) A randomized trial of two dose levels of cyclophosphamide, methotrexate, and fluorouracil chemotherapy for patients with metastatic breast cancer. J Clin Oncol 6:1377–1387CrossRefPubMed
8.
Wood WC, Budman DR, Korzun AH et al (1994) Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med 330:1253–1259CrossRefPubMed
9.
Marschner N, Nagel GA, Beyer JH et al (1990) High-dose epirubicin in combination with cyclophosphamide (HD-EC) in advanced breast cancer: final results of a dose finding study and phase II trial. Onkologie 13:272–278PubMed
10.
Brufman G, Colajori E, Ghilezan N et al (1997) Doubling epirubicin dose intensity (100 mg/m2 versus 50 mg/m2) in the FEC regimen significantly increases response rates. An international randomised phase III study in metastatic breast cancer. The Epirubicin High Dose (HEPI 010) Study Group. Ann Oncol 8:155–162CrossRefPubMed
11.
Fisher B, Anderson S, DeCillis A et al (1999) Further evaluation of intensified and increased total dose of cyclophosphamide for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-25. J Clin Oncol 17:3374–3388CrossRefPubMed
12.
Talbot SM, Westerman DA, Grigg AP et al (1999) Phase I and subsequent phase II study of filgrastim (r-met-HuG-CSF) and dose intensified cyclophosphamide plus epirubicin in patients with non-Hodgkin’s lymphoma and advanced solid tumors. Ann Oncol 10:907–914CrossRefPubMed
13.
Levi JA, Beith JM, Snyder RD et al (1995) Phase II study of high dose epirubicin in combination with cyclophosphamide in patients with advanced breast cancer. Aust New Z J Med 25:474–478CrossRef
14.
Coates A, Gebski V, Bishop JF et al (1987) Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies. N Engl J Med 317:1490–1495CrossRefPubMed
15.
Coates A, Glasziou P, McNeil D (1990) On the receiving end–III. Measurement of quality of life during cancer chemotherapy. Ann Oncol 1:213–217CrossRefPubMed
16.
Spitzer WO, Dobson AJ, Hall J et al (1981) Measuring the quality of life of cancer patients: a concise QL-index for use by physicians. J Chronic Dis 34:585–597CrossRefPubMed
17.
Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observation. J Am Stat Assoc 53:457–481CrossRef
18.
Peto R, Pike MC, Armitage P et al (1977) Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 35:1–39CrossRefPubMedPubMedCentral
19.
Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214CrossRefPubMed
20.
French Epirubicin Study Group (2000) Epirubicin-based chemotherapy in metastatic breast cancer patients: role of dose-intensity and duration of treatment. J Clin Oncol 18:3115–3124CrossRef
21.
Norton L, Simon R, Brereton HD, Bogden AE (1976) Predicting the course of Gompertzian growth. Nature 264:542–545CrossRefPubMed
22.
Norton L, Simon R (1986) The Norton-Simon hypothesis revisited. Cancer Treat Rep 70:163–169PubMed
23.
24.
25.
Chia SK, Speers CH, D’Yachkova Y et al (2007) The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer 110:973–979CrossRefPubMed
26.
Bilgrami S, Feingold JM, Bona RD et al (2000) Dose-intense paclitaxel, etoposide and cyclophosphamide: a safe and active regimen for tumor cytoreduction and stem cell mobilization in metastatic breast cancer. Bone Marrow Transpl 25:123–130CrossRef
27.
Ballestrero A, Montemurro F, Gonella R et al (2003) Dose-dense vinorelbine and paclitaxel with granulocyte colony-stimulating factor in metastatic breast cancer patients: anti-tumor activity and peripheral blood progenitor cell mobilization capability. Breast Cancer Res Treat 82:185–190CrossRefPubMed
28.
Winer EP, Berry DA, Woolf S et al (2004) Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: cancer and leukemia group B trial 9342. J Clin Oncol 22:2061–2068CrossRefPubMed
29.
Berry DA, Ueno NT, Johnson MM et al (2011) High-dose chemotherapy with autologous stem-cell support as adjuvant therapy in breast cancer: overview of 15 randomized trials. J Clin Oncol 29:3214–3223CrossRefPubMedPubMedCentral
30.
Tanner M, Isola J, Wiklund T et al (2006) Topoisomerase IIα gene amplification predicts favorable treatment response to tailored and dose-escalated anthracycline-based adjuvant chemotherapy in HER-2/neu–amplified breast cancer: Scandinavian Breast Group Trial 9401. J Clin Oncol 24:2428–2436CrossRefPubMed
31.
Bastholt L, Dalmark M, Gjedde SB et al (1996) Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer: a randomized study of epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative Group. J Clin Oncol 14:1146–1155CrossRefPubMed
32.
Lalisang RI, Erdkamp FL, Rodenburg CJ et al (2011) Epirubicin and paclitaxel with G-CSF support in first line metastatic breast cancer: a randomized phase II study of dose-dense and dose-escalated chemotherapy. Breast Cancer Res Treat 128:437–445CrossRefPubMed
33.
34.
Berry DA, Ueno NT, Johnson MM et al (2011) High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in metastatic breast cancer: overview of six randomized trials. J Clin Oncol 29:3224–3231CrossRefPubMedPubMedCentral
35.
Petrelli F, Coinu A, Lonati V et al (2016) Neoadjuvant dose-dense chemotherapy for locally advanced breast cancer: a meta-analysis of published studies. Anticancer Drugs 27:702–708CrossRefPubMed
Metadata
Title
Dose intensity in anthracycline-based chemotherapy for metastatic breast cancer: mature results of the randomised clinical trial ANZ 9311
Authors
Stephen. P. Ackland
V. Gebski
N. Zdenkowski
A. Wilson
M. Green
S. Tees
H. Dhillon
G. Van Hazel
J. Levi
R. J. Simes
J. F. Forbes
A. S. Coates
for Breast Cancer Trials Ltd (formerly known as the Australia and New Zealand Breast Cancer Trials Group)
Publication date
01-07-2019
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-019-05187-y

Other articles of this Issue 2/2019

Breast Cancer Research and Treatment 2/2019 Go to the issue

Epidemiology

Does every woman presenting with malignant calcifications require a post lumpectomy mammogram?

Epidemiology

Clinico-pathologic and mammographic characteristics of inflammatory and non-inflammatory breast cancer at six centers in North Africa

Preclinical study

Regulation of AKT phosphorylation by GSK3β and PTEN to control chemoresistance in breast cancer

Clinical trial

Breast desmoid tumor management in France: toward a new strategy

Review

Examining the cost-effectiveness of baseline left ventricular function assessment among breast cancer patients undergoing anthracycline-based therapy

Clinical trial

Establishing physical activity in breast cancer: self-report versus activity tracker
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits