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Different Anthracycline Derivates For Reducing Cardiotoxicity In Cancer Patients.
E. C. van Dalen, E. Michiels, H. Caron, L. Kremer
Published 2010 · Medicine
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BACKGROUND The use of anthracyclines is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been studied. OBJECTIVES To determine the occurrence of cardiotoxicity with the use of different anthracycline derivates in cancer patients. SEARCH STRATEGY We searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 to 29 May 2009) and EMBASE (1980 to 2 June 2009). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing-trials-databases. SELECTION CRITERIA Randomised controlled trials (RCTs) in which different anthracycline derivates were compared in cancer patients (children and adults). DATA COLLECTION AND ANALYSIS Two authors independently performed study selection, assessment of risk of bias and data-extraction including adverse effects. MAIN RESULTS We identified five RCTs of varying quality addressing epirubicin versus doxorubicin (1036 patients) with the same dose. The meta-analysis showed no evidence for a significant difference in the occurrence of clinical heart failure between the treatment groups (RR = 0.36, 95% CI 0.12 to 1.11). However, there is some suggestion of a lower rate of clinical heart failure in patients treated with epirubicin.We identified two RCTs with varying quality addressing liposomal-encapsulated doxorubicin versus conventional doxorubicin (521 patients). The meta-analysis showed a significantly lower rate of both clinical heart failure and clinical and subclinical heart failure combined in patients treated with liposomal-encapsulated doxorubicin (RR = 0.20, 95% CI 0.05 to 0.75 and RR = 0.38, 95% CI 0.24 to 0.59 respectively). It should be noted that in one of the studies patients in the liposomal-encapsulated doxorubicin group received a higher cumulative anthracycline dose than patients in the doxorubicin group.For the other possible combinations of different anthracycline derivates only one RCT (epirubicin versus liposomal-encapsulated doxorubicin) or no RCT was identified. AUTHORS' CONCLUSIONS We are not able to favour either epirubicin or doxorubicin when given with the same dose. Based on the currently available evidence on heart failure, we conclude that in adults with a solid tumour liposomal-encapsulated doxorubicin should be favoured over doxorubicin. For both epirubicin versus doxorubicin and liposomal-encapsulated doxorubicin versus conventional doxorubicin no conclusions can be made about the effects of treatment in children treated with anthracyclines and also not in patients diagnosed with leukaemia. More research is needed. For other combinations of anthracycline derivates not enough evidence was available to make definitive conclusions about the occurrence of cardiotoxicity in patients treated with anthracyclines.
This paper references
Comparison of CHOP-B vs CEOP-B in ‘poor prognosis’ non-Hodgkin’s lymphomas. A randomized trial
M. Lena (1989)
Prognostic Subgroups: The Key Factor for Treatment Outcome in Metastatic Breast Cancer
E. Heidemann (1993)
A randomized comparison of single-agent doxorubicin and epirubicin as first-line cytotoxic therapy in advanced breast cancer.
D. Perez (1991)
A randomized trial comparing the effect of epirubicin and doxorubicin in soft tissue sarcoma
H. Pinedo (1987)
Pegylated Liposomal Doxorubicin (Doxil®) Versus Doxorubicin for First-Line Treatment of Metastatic Breast Cancer
K. Maung (2002)
Cardiac toxicity of adriamycin-DNA complex and rubidazone: evaluation by electrocardiogram and endomyocardial biopsy.
R. Benjamin (1978)
A randomized comparison of the efficacy and toxicity of epirubicin and doxorubicin in the treatment of patients with non‐hodgkin's lymphoma
R. Nair (1998)
Comparison of epirubicin and doxorubicin cardiotoxicity in children and adolescents treated within the German Cooperative Soft Tissue Sarcoma Study (CWS)
W. Stöhr (2005)
A comparison of doxorubicin, epirubicin and mitozantrone as single agents in advanced breast carcinoma.
P. Lawton (1993)
Daunorubicin and adriamycin in the treatment of leukemia.
P. Klener (1973)
Randomised trial comparing combinations of cyclophosphamide and cisplatin without or with doxorubicin or 4′‐epi‐doxorubicin in the treatment of advanced ovarian cancer
Z. Hernádi (1988)
Appraising cardiotoxicity associated with liposomal doxorubicin by means of tissue Doppler echocardiography end-points: rationale and design of the LITE (Liposomal doxorubicin-Investigational chemotherapy-Tissue Doppler imaging Evaluation) randomized pilot study.
M. Lotrionte (2009)
Cardiotoxicity of Cancer Chemotherapy
Valeriano C. Simbre (2005)
Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial.
G. Ambrosini (1988)
Frequency and risk factors of subclinical cardiotoxicity after anthracycline therapy in children: a systematic review.
L. Kremer (2002)
Results of a phase III prospective, randomised trial, comparing mitoxantrone and vinorelbine (MV) in combination with standard FAC/FEC in front-line therapy of metastatic breast cancer.
M. Namer (2001)
Clinical heart failure in a cohort of children treated with anthracyclines: a long-term follow-up study.
E. C. van Dalen (2006)
New anthracycline antitumor antibiotics.
F. Muggia (1991)
Improved treatment results in high-risk pediatric acute myeloid leukemia patients after intensification with high-dose cytarabine and mitoxantrone: results of Study Acute Myeloid Leukemia-Berlin-Frankfurt-Münster 93.
U. Creutzig (2001)
Evaluation of long term cardiotoxicity after epirubicin containing adjuvant chemotherapy and locoregional radiotherapy for breast cancer using various detection techniques
M. T. Meinardi (2002)
Randomized Comparison of Cisplatin plus Epirubicin or Doxorubicin for Advanced Epithelial Ovarian Carcinoma: A Multicenter Trial
H. Homesley (1992)
Die französische FAC-vs-FEC-Studie bei fortgeschrittenen Mammakarzinomen
R. Keiling (1986)
High-dose epirubicin is not an alternative to standard-dose doxorubicin in the treatment of advanced soft tissue sarcomas. A study of the EORTC soft tissue and bone sarcoma group.
O. Nielsen (1998)
editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.0 [updated February 2009
JPT Higgins 2009 Higgins (2009)
Pharmacokinetics of doxorubicin administered i.v. as Myocet (TLC D-99; liposome-encapsulated doxorubicin citrate) compared with conventional doxorubicin when given in combination with cyclophosphamide in patients with metastatic breast cancer
C. Swenson (2003)
Anthracycline-induced clinical heart failure in a cohort of 607 children: long-term follow-up study.
L. Kremer (2001)
Long-term results of combined-modality therapy for inflammatory breast carcinoma.
E. Baldini (2004)
Comparison of epirubicin and doxorubicin cardiotoxicity induced by low doses: Evolution of the diastolic and systolic parameters studied by radionucide angiography
Y. Cottin (1998)
Doxorubicin vs epirubicin, report of a second-line randomized phase II/III study in advanced breast cancer. EORTC Breast Cancer Cooperative Group.
M. Bontenbal (1998)
Frequency and risk factors of anthracycline-induced clinical heart failure in children: a systematic review.
L. Kremer (2002)
Results of a randomized study of early stage Hodgkin's disease using ABVD, EBVD, or MBVD.
A. Avilés (1995)
Anticancer agents and cardiotoxicity.
R. Ng (2006)
Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer.
M. O'Brien (2004)
Treatment of advanced ovarian cancer: a randomised trial comparing adriamycin or 4'epi-adriamycin in combination with cisplatin and cyclophosphamide.
W. Bezwoda (1986)
Combined NT-pro-BNP and CW-Doppler ultrasound cardiac output monitoring (USCOM) in epirubicin and liposomal doxorubicin therapy.
K. Knobloch (2008)
Adriamycin versus epirubicin in advanced soft tissue sarcomas. A randomized phase II/phase III study of the EORTC Soft Tissue and Bone Sarcoma Group.
H. Mouridsen (1987)
Doxorubicin and 4'-epidoxorubicin in combination chemotherapy of extensive small cell lung cancer.
T. Nikkanen (1988)
Liposomal daunorubicin versus standard daunorubicin: long term follow‐up of the GIMEMA GSI 103 AMLE randomized trial in patients older than 60 years with acute myelogenous leukaemia
R. Latagliata (2008)
Epidoxorubicin vs idarubicin containing regimens in intermediate and high grade non-Hodgkin's lymphoma: preliminary results of a multicentric randomized trial.
M. Brugiatelli (1993)
Cardiac toxicity of daunorubicin.
G. Bonadonna (1969)
Doxorubicin Encapsulated in Liposomes Containing Surface‐Bound Polyethylene Glycol: Pharmacokinetics, Tumor Localization, and Safety in Patients with AIDS‐Related Kaposi's Sarcoma
D. Northfelt (1996)
Phase III trial of liposomal doxorubicin and cyclophosphamide compared with epirubicin and cyclophosphamide as first-line therapy for metastatic breast cancer.
S. Chan (2004)
Late cardiac toxicity of doxorubicin, epirubicin, and mitoxantrone therapy for Hodgkin's disease in adults.
A. Avilés (1993)
A Comparative Study of Doxorubicin and Epirubicin in Patients with Metastatic Breast Cancer
G. Hortobagyi (1989)
Cardiotoxicity of epirubicin versus doxorubicin: cost and clinical results.
G. Ventura (2005)
Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.
M. K. Parmar (1998)
Late non-neoplastic events in patients with aggressive non-Hodgkin's lymphoma in four randomized European Organisation for Research and Treatment of Cancer trials.
E. Moser (2005)
Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.
K. Schulz (1995)
Randomized study comparing 4′‐epi‐doxorubicin (Epirubicin) versus doxorubicin as a part of induction treatment in adult acute lymphoblastic leukemia
M. Bhutani (2002)
Epirubicin is not Superior to Doxorubicin in the Treatment of Advanced Soft Tissue Sarcomas.The Experience of the EORTC Soft Tissue and Bone Sarcoma Group
O. Nielsen (2000)
Randomized trial with two CHOP-B regimens (with doxorubicin or epirubicin) in poor prognosis non-Hodgkin's lymphomas
M. Lena (1987)
Anthracycline cardiomyopathy monitored by morphologic changes.
M. Billingham (1978)
Combination chemotherapy including epirubicin for the management of non-Hodgkin's lymphoma.
S. A. Al‐Ismail (1987)
Phase III comparative trial using CHOP vs CIOP in the treatment of advanced intermediate-grade non-Hodgkin's lymphoma.
P. Zinzani (1995)
New anthracycline analogs in advanced breast cancer.
V. Bonfante (1986)
Weekly Epirubicin Versus Doxorubicin as Second Line Therapy in Advanced Breast Cancer A Randomized Clinical Trial
G. Gasparini (1991)
A randomised clinical trial comparing idarubicin and cytarabine to daunorubicin and cytarabine in the treatment of acute non-lymphoid leukaemia
F. Mandelli (1991)
Late cardiac toxicity secondary to treatment in Hodgkin's disease. A study comparing doxorubicin, epirubicin and mitoxantrone in combined therapy
A. Avilés (2005)
K. Shan (1996)
Cochrane Handbook for Systematic Reviews of Interventions
Michele Tarsilla (2010)
Idarubicin in patients with diffuse large cell lymphomas: a randomized trial comparing VACOP-B (A = doxorubicin) vs VICOP-B (I = idarubicin).
M. Bertini (1997)
Different anthracycline derivates for reducing cardiotoxicity in cancer patients.
E. C. van Dalen (2006)
Verbesserung der Prognose bei Kindern mit AML: Ergebnisse der Studie AML-BFM 93
U. Creutzig (2001)
Efficacy of two different ProMACE-CytaBOM derived regimens in advanced aggressive non-Hodgkin's lymphoma. Final report of a multicenter trial conducted by GISL.
M. Federico (1998)
Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93
U. Creutzig (2001)
5-Fluorouracil, adriamycin, cyclophosphamide (FAC) vs. 5-fluorouracil, epirubicin, cyclophosphamide (FEC) in metastatic breast cancer.
M. Lopez (1989)
Induction chemotherapy with ifosfamide, etoposide, and anthracycline for small cell lung cancer: experience of the European Lung Cancer Working Party.
J. Sculier (1995)
Reporting results of cancer treatment
A. Miller (1981)
Cardiotoxicity of epirubicin and doxorubicin: A double‐blind randomized study
R. Lahtinen (1991)
[Therapy realization and complications in the BFM-83 therapy study of acute myelogenous leukemia].
U. Creutzig (1988)
Liposome‐encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first‐line therapy of metastatic breast carcinoma
L. Harris (2002)
Combining platinum, paclitaxel and anthracycline in patients with advanced gynaecological malignancy.
R. Gregory (2000)
Comparison of CHOP versus CIOP in good prognosis younger patients with histologically aggressive non‐Hodgkin lymphoma
C. Burton (2005)
Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma
R. Rifkin (2006)
Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer.
G. Batist (2001)
Early decline in left ventricular ejection fraction predicts doxorubicin cardiotoxicity in lymphoma patients
T. Nousiainen (2002)
WHO Handbook for Reporting Results of Cancer Treatment
R. Hunter (1980)
A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer.
K. K. Jain (1985)
A clinicopathologic analysis of adriamycin cardiotoxicity
E. Lefrak (1973)
This paper is referenced by
Nanotechnology-based Strategies To Enhance Chemo-and Radiation Therapy In Breast Cancer
Preethy Prasad (2014)
Cardioprotective strategies to prevent breast cancer therapy-induced cardiotoxicity.
Allison Padegimas (2019)
Long-term cardiac and pulmonary complications of cancer therapy.
J. Yahalom (2008)
Nanomedicines in the future of pediatric therapy.
A. Sosnik (2014)
Cardiac effects of anticancer therapy in the elderly.
M. Accordino (2014)
Histology-Driven Chemotherapy in Soft Tissue Sarcomas
M. Scurr (2011)
Improving the therapeutic index of anthracycline chemotherapy: focus on liposomal doxorubicin (Myocet).
R. Leonard (2009)
Molecular Mechanisms of Anthracycline-Induced Cardiotoxicity
R. Moudgil (2017)
Multistage delivery of chemotherapeutic nanoparticles for breast cancer treatment.
E. Blanco (2013)
Cardiotoxicity of anticancer treatments
M. Ewer (2015)
Survivorship - lebenslange Begleitung von Krebspatienten
Eva-Maria Kalusche-Bontemps (2015)
A nem pegilált liposzomális doxorubicin (Myocet®), mint a szabad doxorubicin kevésbé kardiotoxikus alternatívája
T. Nagykálnai (2010)
Cardiotoxicity in Children
F. Cairello (2017)
The Role of Liposomal Anthracyclines in Metastatic Breast Cancer
A. Gennari (2013)
Late Mortality After Dexrazoxane Treatment: A Report From the Children's Oncology Group.
E. Chow (2015)
Non-pegylated liposome-encapsulated doxorubicin citrate plus cyclophosphamide or vinorelbine in metastatic breast cancer not previously treated with chemotherapy:a multicenter phase III study.
V. Lorusso (2014)
Angela Y. Higgins (2015)
Prognostic factors and late effects of treatment in localised high grade extremity osteosarcoma
J. Bramer (2010)
Prediction of cardiovascular disease among hematopoietic cell transplantation survivors.
S. Armenian (2018)
hematopoietic cell transplantation Incidence and predictors of congestive heart failure following autologous
Florence L. Wong (2012)
Bernard I. Lévy (2013)
A Review of the Cardiovascular Effects of Oncology Agents
Bradi L. Frei (2008)
Two multicenter Phase I randomized trials to compare the bioequivalence and safety of a generic doxorubicin hydrochloride liposome injection with Doxil® or Caelyx® in advanced ovarian cancer
Shravanti Bhowmik (2018)
A Novel Lipid-based Nanotechnology Platform For Biomedical Imaging And Breast Cancer Chemotherapy
Adam J Shuhendler (2013)
Myocardial Protection During Cardiotoxic Chemotherapy.
R. Witteles (2015)
Effectiveness and tolerability of neoadjuvant pertuzumab-containing regimens for HER2-positive localized breast cancer
L. Spring (2018)
Cardio-Oncology: An Update on Cardiotoxicity of Cancer-Related Treatment.
C. Lenneman (2016)
Estrategias de cardioprotección; ¿mantienen la efectividad de la quimioterapia? Strategies of cardioprotection; is effectiveness of chemotherapy affected?
A. S. Olvera (2009)
Childhood cancer survivors: The integral role of the cardiologist and cardiovascular imaging.
Wendy J Bottinor (2020)
Cardiovascular Complications of Cancer Therapeutics
A. Khakoo (2011)
Witteles and Bosch Myocardial Protection During Cardiotoxic Chemotherapy 1837
R. Witteles ()
Prevalence and predictors of anthracycline cardiotoxicity in children treated for acute myeloid leukaemia: Retrospective cohort study in a single centre in the United Kingdom
P. Temming (2011)See more