Online citations, reference lists, and bibliographies.
← Back to Search

Improved Anti-tumor Response Rate With Decreased Cardiotoxicity Of Non-pegylated Liposomal Doxorubicin Compared With Conventional Doxorubicin In First-line Treatment Of Metastatic Breast Cancer In Patients Who Had Received Prior Adjuvant Doxorubicin: Results Of A Retrospective Analysis

G. Batist, L. Harris, N. Azarnia, L. W. Lee, P. Daza-Ramirez
Published 2006 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
Our objectives were to ascertain the safety (cardiotoxicity) and efficacy of non-pegylated liposomal doxorubicin [Myocet (M)] compared with conventional doxorubicin (A) in patients with metastatic breast cancer (MBC) who had received adjuvant anthracycline treatment and were at high risk of developing iatrogenic cardiomyopathy. This retrospective analysis is based on data pooled from two prospective phase III comparative randomized clinical trials comparing Myocet versus conventional doxorubicin in combination with cyclophosphamide and as single agents, respectively, for the treatment of MBC. The outcome measures reviewed in this analysis were overall response, time to treatment failure, time to disease progression, overall survival and cardiotoxicity. The analysis was carried out by strata according to patients' previous exposure to adjuvant anthracyclines. Kaplan–Meier, log-rank χ2-test, Cox proportional-hazards and Cochran–Mantel–Haenszel statistics were used for the analysis. Sixty-eight patients were included in this analysis: 29 and 39 patients from Studies 1 and 2, respectively, had received adjuvant anthracycline treatment. Study 1, with n=297, compared M 60 mg/m2 (M60) plus cyclophosphamide (C) 600 mg/m2 (C600) versus A 60 mg/m2 (A60) plus C600 as first-line treatment for MBC. Twenty-nine patients had received prior adjuvant doxorubicin, of whom, after randomization, 14 received M60+C600 and 15 received A60+C600 for the treatment of MBC. Study 2, with n=224, compared M 75 mg/m2 (M75) with A 75 mg/m2 (A75) as first-line treatment for MBC disease. Thirty-nine patients had received prior adjuvant doxorubicin, of whom, after randomization, 18 received M75 and 21 received A75 for their MBC. Hence, 32 patients received M-containing regimens and 36 received A-containing regimens for the treatment of MBC. Median age in both groups was 54 years. The groups were well balanced in terms of demographic characteristics. Overall response rates were 31% and 11% for M-treated patients and A-treated patients, respectively (Cochran–Mantel–Haenszel P=0.04, odds ratio=4.0). Median time to progression was 4.5 versus 3.4 months [log-rank P=0.66, hazard ratio (HR)=1.14], median time to treatment failure was 4.2 versus 2.1 months (log-rank P=0.01, HR=2.06) and median survival time was 16 versus 15 months (log-rank P=0.71, HR=1.12). Cardiac events occurred in 22% of M-treated patients [one congestive heart failure (CHF)] versus 39% of A-treated patients (three CHFs) (log-rank, P=0.001). Median lifetime dose at onset of cardiotoxicity was 780 mg/m2 for M versus 580 mg/m2 for A (log-rank P=0.001, HR=4.8). This retrospective analysis shows that treatment based on non-pegylated liposomal doxorubicin (Myocet) significantly reduced the risk of cardiotoxicity in patients with MBC who had received prior adjuvant doxorubicin. Furthermore, anti-tumor activity and time to treatment failure were significantly improved compared with patients who received treatment based on conventional doxorubicin for their MBC. This analysis revisits the therapeutic option of including doxorubicin in the treatment of MBC patients who have had prior adjuvant anthracycline exposure.
This paper references
10.1016/S0960-9776(01)80001-1
Liposome technology and the development of Myocet™ (liposomal doxorubicin citrate)
C. Swenson (2001)
10.1093/ANNONC/MDF157
EORTC 10968: a phase I clinical and pharmacokinetic study of polyethylene glycol liposomal doxorubicin (Caelyx, Doxil) at a 6-week interval in patients with metastatic breast cancer. European Organization for Research and Treatment of Cancer.
A. Hamilton (2002)
10.1200/JCO.1988.6.6.976
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)
10.1200/JCO.2003.08.013
Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: an intergroup trial (E1193).
G. Sledge (2003)
Myocet (liposomeencapsulated doxorubicin citrate): a new approach in breast cancer therapy
G Batist (2002)
10.1200/JCO.1989.7.5.560
Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer.
I. C. Henderson (1989)
Pegylated liposomal doxorubicin ( doxil ) : Reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg / m 2
iT. Safra (2005)
10.1200/JCO.1997.15.4.1318
Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer.
S. Swain (1997)
10.1200/JCO.1999.17.8.2341
Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer.
S. Chan (1999)
10.7326/0003-4819-91-5-710
Risk factors for doxorubicin-induced congestive heart failure.
D. V. Von Hoff (1979)
10.1016/J.CTRV.2004.06.002
Evaluating the role of dexrazoxane as a cardioprotectant in cancer patients receiving anthracyclines.
P. Pouillart (2004)
Updated results of a phase II study (M77035) of Myocet combined with weekly Herceptin and paclitaxel in patients with HER2-positive locally advanced or metastatic breast cancer
J Cortes (2004)
10.1200/JCO.2000.18.12.2385
Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group Study MA8.
B. Norris (2000)
10.1517/14656566.3.12.1739
Myocet (liposome-encapsulated doxorubicin citrate): a new approach in breast cancer therapy
G. Batist (2002)
10.1200/JCO.2004.08.157
Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer.
Alan M. Keller (2004)
Comparison of the cardiotoxic effects of liposomal doxorubicin versus free doxorubicin in beagle dogs
PM Kanter (1993)
10.1001/ARCHDERM.136.12.1475
Skin toxic effects of polyethylene glycol-coated liposomal doxorubicin.
M. Lotem (2000)
Adriamycin s (doxorubicin hydrochloride) US full prescribing information
Pharmacia (2000)
10.1200/JCO.1988.6.10.1611
A randomized multicenter trial comparing mitoxantrone, cyclophosphamide, and fluorouracil with doxorubicin, cyclophosphamide, and fluorouracil in the therapy of metastatic breast carcinoma.
J. Bennett (1988)
Liposomeencapsulated doxorubicin compared with conventional doxorubicin in a randomized multicentre trial as first-line therapy of metastatic breast carcinoma
L Harris (2002)
10.1200/jco.1988.6.4.679
A prospective randomized phase III trial comparing combination chemotherapy with cyclophosphamide, fluorouracil, and either doxorubicin or epirubicin. French Epirubicin Study Group.
(1988)
Comparison of the cardiotoxic effects of liposomal doxorubicin (TLC D-99) versus free doxorubicin in beagle dogs.
P. M. Kanter (1993)
10.1097/00001813-200303000-00008
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)
10.1056/NEJMOA035153
The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia.
S. Lipshultz (2004)
Updated results of a phase II study ( M 77035 ) of Myocet combined with weekly Herceptin and paclitaxel in patients with HER 2 - positive locally advanced or metastatic breast cancer ( LABC / MBC )
J Cortes
10.1093/JNCI/83.15.1077
Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study.
J. D. Cowan (1991)
10.1200/JCO.2000.18.4.724
Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over.
R. Paridaens (2000)
10.1016/0002-9343(87)90212-9
Congestive heart failure and left ventricular dysfunction complicating doxorubicin therapy. Seven-year experience using serial radionuclide angiocardiography.
R. G. Schwartz (1987)
10.1002/cncr.10201
Liposome‐encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first‐line therapy of metastatic breast carcinoma
L. Harris (2002)
10.1200/JCO.2001.19.5.1444
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)
10.1007/BF00273522
Analysis of the effect of liposome encapsulation on the vesicant properties, acute and cardiac toxicities, and antitumor efficacy of doxorubicin
J. Balazsovits (2004)
10.1016/0960-9776(93)90027-D
The aetiology of periductal mastitis
N. Bundred (1993)
Adriamycin cardiotoxicity: a survey of 1273 patients.
C. Praga (1979)
Phase III randomized study of fluorouracil , epirubicin , and cyclophosphamide v fluorouracil , doxorubicin , and cyclophosphamide in advanced breast cancer
JM Bennett (1988)
10.1023/A:1008365716693
Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2.
T. Safra (2000)



This paper is referenced by
10.1097/CRD.0b013e3181b8e4c8
Pharmacologic Prevention of Anthracycline-Induced Cardiomyopathy
Kuldeep Maradia (2009)
10.1016/S1359-6349(11)70004-0
Anthracyclines in the management of metastatic breast cancer: state of the art
A. Gennari (2011)
10.1016/j.ijpharm.2008.01.041
Tumor-specific antibody-mediated targeted delivery of Doxil reduces the manifestation of auricular erythema side effect in mice.
T. Elbayoumi (2008)
10.1634/THEONCOLOGIST.12-7-785
First-line treatment options for patients with HER-2 negative metastatic breast cancer: the impact of modern adjuvant chemotherapy.
S. Verma (2007)
10.1093/annonc/mdn663
Phase I clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neo-adjuvant treatment in stages II and IIIA, HER2-overexpressing breast cancer patients. GEICAM 2003-03 study.
A. Antón (2009)
10.1002/pds.1376
Current awareness: Pharmacoepidemiology and drug safety
(2007)
10.1016/j.breast.2009.05.004
Improving the therapeutic index of anthracycline chemotherapy: focus on liposomal doxorubicin (Myocet).
R. Leonard (2009)
10.1177/030089160909500402
Non-Pegylated Liposomal Doxorubicin in Combination with Cyclophosphamide or Docetaxel as First-Line Therapy in Metastatic Breast Cancer: A Retrospective Analysis
L. Livi (2009)
10.1634/THEONCOLOGIST.12-11-1288
First-line chemotherapy for HER-2 negative metastatic breast cancer patients who received anthracyclines as adjuvant treatment.
A. Morabito (2007)
10.1007/s12609-012-0099-z
The Role of Liposomal Anthracyclines in Metastatic Breast Cancer
A. Gennari (2013)
10.14499/INDONESIANJCANCHEMOPREV9ISS2PP68-77
Anti-metastatic Profiles of Boesenbergia pandurata towards MCF-7/HER2 Cells
Hilyatul Fadliyah (2018)
10.1093/ANNONC/MDM229
Role of liposomal anthracyclines in breast cancer.
V. Lorusso (2007)
Stanowisko w sprawie stosowania niepegylowanej liposomalnej doksorubicyny u chorych na chłoniaki ze współistniejącymi chorobami sercowo-naczyniowymi
Sebastian Szmit (2013)
10.1586/14737140.8.12.1859
Efficacy and toxicity of nonpegylated liposomal doxorubicin in breast cancer
Flora Stavridi (2008)
10.2217/fca.15.28
Heart failure and chemotherapeutic agents.
S. Piper (2015)
10.4172/2157-7439.1000197
The Influence of Drug Loading on Caveolin-1 Mediated Intracellular Internalization of Doxorubicin Nanomicelles in vitro
H. Nehoff (2014)
10.1556/MONKOL.54.2010.4.10
A nem pegilált liposzomális doxorubicin (Myocet®), mint a szabad doxorubicin kevésbé kardiotoxikus alternatívája
T. Nagykálnai (2010)
10.1111/ddg.12012_suppl
Therapie der fortgeschrittenen kutanen T‐Zell‐Lymphome mit nichtpegyliertem liposomalem Doxorubicin – Konsensus der Lymphomgruppe der Arbeitsgemeinschaft Dermatologische Onkologie
C. Assaf (2013)
10.1016/j.clbc.2013.10.011
Multicenter experience of nonpegylated liposomal doxorubicin use in the management of metastatic breast cancer.
C. Palmieri (2014)
10.1007/s10549-008-0218-8
Non-pegylated liposomal doxorubicin combined with gemcitabine as first-line treatment for metastatic or locally advanced breast cancer. Final results of a phase I/II trial
S. Barco (2008)
Pegylated or non-pegylated liposomal doxorubicin in the management of advanced breast cancer : a meta-analysis
M. Huang (2016)
10.2217/17455057.3.5.557
Liposomal Doxorubicin in Breast Cancer
M. Shehata (2007)
10.1038/s41598-020-75614-4
Predictors of new-onset heart failure and overall survival in metastatic breast cancer patients treated with liposomal doxorubicin
S. Szmit (2020)
10.1007/978-1-4020-8369-3_29
Chemotherapy for Metastatic Breast Cancer Patients Who Received Adjuvant Anthracyclines (An Overview)
A. Morabito (2008)
10.1155/2013/456409
Liposomal Doxorubicin in the Treatment of Breast Cancer Patients: A Review
J. Lao (2013)
10.1016/S1359-6349(11)70008-8
Case histories: breast cancer
A. Gennari (2011)
10.1016/j.ijpharm.2017.01.002
Distinct biodistribution of doxorubicin and the altered dispositions mediated by different liposomal formulations.
Ruijuan Luo (2017)
10.1007/s12094-012-0954-4
Safety and efficacy of metronomic non-pegylated liposomal encapsulated doxorubicin in heavily pretreated advanced breast cancer patients
L. Manso (2012)
10.1097/RLI.0b013e31828328d7
Magnetic Resonance–Guided Laser-Induced Interstitial Thermotherapy of Breast Cancer Liver Metastases and Other Noncolorectal Cancer Liver Metastases: An Analysis of Prognostic Factors for Long-Term Survival and Progression-Free Survival
T. Vogl (2013)
10.1016/j.breast.2010.05.008
Non-pegylated liposomal doxorubicin in metastatic breast cancer patients: a valuable therapeutic option requiring caution.
D. Bernardi (2010)
10.5603/KP.2016.0127
[Liposomal doxorubicin in patients with breast cancer and concomitant cardiovascular diseases - interdisciplinary expert opinion].
S. Szmit (2016)
10.2147/bctt
Breast Cancer: Targets and Therapy
I. Macpherson (2009)
See more
Semantic Scholar Logo Some data provided by SemanticScholar