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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, N. Wigler, M. Inbar, R. Rosso, E. Grischke, A. Santoro, R. Catane, D. G. Kieback, P. Tomczak, S. P. Ackland, F. Orlandi, L. Mellars, L. Alland, C. Tendler
Published 2004 · Medicine

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BACKGROUND This study was designed to demonstrate that efficacy [progression-free survival (PFS)] of CAELYX [pegylated liposomal doxorubicin HCl (PLD)] is non-inferior to doxorubicin with significantly less cardiotoxicity in first-line treatment of women with metastatic breast cancer (MBC). PATIENTS AND METHODS Women (n=509) with MBC and normal cardiac function were randomized to receive either PLD 50 mg/m2 (every 4 weeks) or doxorubicin 60 mg/m2 (every 3 weeks). Cardiac event rates were based on reductions in left ventricular ejection fraction as a function of cumulative anthracycline dose. RESULTS PLD and doxorubicin were comparable with respect to PFS [6.9 versus 7.8 months, respectively; hazard ratio (HR)=1.00; 95% confidence interval (CI) 0.82-1.22]. Subgroup results were consistent. Overall risk of cardiotoxicity was significantly higher with doxorubicin than PLD (HR=3.16; 95%CI 1.58-6.31; P<0.001). Overall survival was similar (21 and 22 months for PLD and doxorubicin, respectively; HR=0.94; 95%CI 0.74-1.19). Alopecia (overall, 66% versus 20%; pronounced, 54% versus 7%), nausea (53% versus 37%), vomiting (31% versus 19%) and neutropenia (10% versus 4%) were more often associated with doxorubicin than PLD. Palmar-plantar erythrodysesthesia (48% versus 2%), stomatitis (22% versus 15%) and mucositis (23% versus 13%) were more often associated with PLD than doxorubicin. CONCLUSIONS In first-line therapy for MBC, PLD provides comparable efficacy to doxorubicin, with significantly reduced cardiotoxicity, myelosuppression, vomiting and alopecia.
This paper references
Doxorubicin-induced cardiomyopathy.
P. Singal (1998)
Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2.
T. Safra (2000)
Risk factors for doxorubicin-induced congestive heart failure.
D. V. Von Hoff (1979)
Combination versus sequential single agent chemotherapy in advanced breast cancer: associations with metastatic sites and long-term survival. The Western Cancer Study Group and The Southeastern Cancer Study Group.
R. Chlebowski (1989)
Caelyx in malignant mesothelioma: a phase II EORTC study.
P. Baas (2000)
Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan.
A. Gordon (2001)
Efficacy of pyridoxine to ameliorate the cutaneous toxicity associated with doxorubicin containing pegylated (Stealth) liposomes: a randomized, double-blind clinical trial using a canine model.
D. Vail (1998)
Liposome‐encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first‐line therapy of metastatic breast carcinoma
L. Harris (2002)
Combination chemotherapy versus single-agent therapy as first- and second-line treatment in metastatic breast cancer: a prospective randomized trial.
H. Joensuu (1998)
New treatments for breast cancer.
G. Smith (1996)
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)
A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer.
K. K. Jain (1985)
Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial.
M. Ranson (1997)
Selective delivery of doxorubicin to patients with breast carcinoma metastases by stealth liposomes
Z. Symon (1999)
Reporting results of cancer treatment
A. Miller (1981)
Phase II trial of the pegylated liposomal doxorubicin in previously treated metastatic endometrial cancer: a Gynecologic Oncology Group study.
F. Muggia (2002)
AJCC Cancer Staging Manual
M. B. Amin (2002)
Cardiotoxicity of epirubicin and doxorubicin: assessment by endomyocardial biopsy.
F. Torti (1986)
Polyethylene glycol-coated (pegylated) liposomal doxorubicin. Rationale for use in solid tumours.
A. Gabizon (1997)
Phase II study of liposomal doxorubicin in advanced gynecologic cancers.
V. P. Israel (2000)
Polychemotherapy for early breast cancer: an overview of the randomised trials
M. Clarke (1998)

This paper is referenced by
Efficacy and toxicity of the novel chemotherapeutic agent KW-2170 in recurrent epithelial ovarian cancer.
J. M. Estes (2006)
Pegylated Liposomal Doxorubicin
G. Plosker (2012)
Liposomal doxorubicin and nab-paclitaxel: nanoparticle cancer chemotherapy in current clinical use.
Alexander Gaitanis (2010)
In vitro validation of multifunctional liposomes for leukaemia and prostate cancer therapy - the folate receptor and the prostate-specific membrane antigen as targets for drug delivery
Ida Mostrøm Nilssen (2012)
A Revolution in Nanomedicines
Iulian Bobe (2013)
Intelligent nanomaterials for medicine: carrier platforms and targeting strategies in the context of clinical application.
R. Lehner (2013)
Combination liposome-based anti-cancer preparations
Shravan Kumar Sriraman (2016)
Title Engineered Hybrid Nanoparticles for On-DemandDiagnostics and Therapeutics
Kim Truc Nguyen (2019)
Polymeric Nanocarriers for Treatment of Melanoma and Genetically Modified Mesenchymal Stem Cells to Improve Outcome of Islet Transplantation
Vaibhav Mundra (2015)
Efficiency against multidrug resistance by co-delivery of doxorubicin and curcumin with a legumain-sensitive nanocarrier
Sen Lin (2018)
Clinical benefits and economic analysis of pegylated liposomal doxorubicin/vincristine/dexamethasone versus doxorubicin/vincristine/dexamethasone in patients with newly diagnosed multiple myeloma.
C. A. Porter (2007)
Anticancer agents and cardiotoxicity.
R. Ng (2006)
A Derivate of the Antibiotic Doxorubicin Is a Selective Inhibitor of Dengue and Yellow Fever Virus Replication In Vitro
S. Kaptein (2010)
Imaging-assisted anticancer nanotherapy
Anshuman Dasgupta (2020)
Cardiac Safety of Pegylated Liposomal Doxorubicin (Doxil®/Caelyx®) Demonstrated by Endomyocardial Biopsy in Patients with Advanced Malignancies
A. Gabizon (2004)
Anthracycline- and/or taxane-resistant breast cancer: results of a literature review to determine the clinical challenges and current treatment trends.
A. Moreno-Aspitia (2009)
Safety of nanoparticles : from manufacturing to medical applications
T. Webster (2009)
Elucidating the Influence of Tumor Presence on the Polymersome Circulation Time in Mice
R. M. de Kruijff (2019)
Effects of doxorubicin on the structural and morphological characterization of solid lipid nanoparticles (SLN) using small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS)
F. Yokaichiya (2017)
Captopril improves tumor nanomedicine delivery by increasing tumor blood perfusion and enlarging endothelial gaps in tumor blood vessels.
B. Zhang (2017)
Doxorubicin and liposomal doxorubicin induce senescence by enhancing nuclear factor kappa B and mitochondrial membrane potential.
Marjan Fallah (2019)
The effect of injected dose on localized tumor accumulation and cardiac uptake of doxorubicin in a Vx2 rabbit tumor model using MR-HIFU mild hyperthermia and thermosensitive liposomes.
B. Cheng (2020)
Targeted Nanotherapeutics Encapsulating Liver X Receptor Agonist GW3965 Enhance Antiatherogenic Effects without Adverse Effects on Hepatic Lipid Metabolism in Ldlr−/− Mice
Mikyung Yu (2017)
Nanogel Carrier Design for Targeted Drug Delivery.
D. Eckmann (2014)
Nanostructured Lipid Carrier Co-loaded with Doxorubicin and Docosahexaenoic Acid as a Theranostic Agent: Evaluation of Biodistribution and Antitumor Activity in Experimental Model
R. S. Fernandes (2017)
Investigation of Hexadecylphosphocholine (miltefosine) usage in Pegylated liposomal doxorubicin as a synergistic ingredient: In vitro and in vivo evaluation in mice bearing C26 colon carcinoma and B16F0 melanoma.
M. Teymouri (2015)
Liposome‐induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome‐encapsulated alendronate☆
R. Rajan (2018)
Nanoscale metal–organic frameworks as key players in the context of drug delivery: evolution toward theranostic platforms
C. Carrillo-Carrión (2019)
Simulation of Stimuli-Responsive and Stoichiometrically Controlled Release Rate of Doxorubicin from Liposomes in Tumor Interstitial Fluid
E. Yamamoto (2018)
Extracellular vesicles as natural therapeutic agents and innate drug delivery systems for cancer treatment: Recent advances, current obstacles, and challenges for clinical translation.
Marco Pirisinu (2020)
Liposomal encapsulation masks genotoxicity of a chemotherapeutic agent in regulatory toxicology assessments.
J. Alexander (2017)
Defining the optimal sequence for the systemic treatment of metastatic breast cancer
J. Mestres (2016)
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