scholarly journals Liposomal Doxorubicin in Breast Cancer

2007 ◽  
Vol 3 (5) ◽  
pp. 557-569 ◽  
Author(s):  
M Shehata ◽  
A Mukherjee ◽  
R Sharma ◽  
S Chan
Keyword(s):  
Breast Cancer ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Toxicity Profile ◽  
Pivotal Phase ◽  
Liposomal Formulations ◽  
Phase Iii Trials ◽  
Relative Differences

Drug-delivery carriers represent an important step in the development of targeted therapy. Encapsulation of drug into liposomes represents such a carrier, and helps to minimize side effects of conventional doxorubicin by improving the tumor-specific biodistribution profile. We review the development of the two liposomal doxorubicin formulations, pegylated liposomal doxorubicin and liposomal-encapsulated doxorubicin citrate from reconstitution and comparative pharmacokinetics to pivotal Phase III trials, with special emphasis in breast cancer. The relative differences in the toxicity profile can be attributed to their differences in the liposomal formulations. Areas of special interest include the reduction in cardiac toxicities and the improved efficacy, such as in the treatment of ovarian cancer. These improvements have also increased the potential of these liposomal formulations of doxorubicin for combination and sequencing with other biological and cytotoxic agents for clinical benefit.

scholarly journals Anthracyclines Strike Back: Rediscovering Non-Pegylated Liposomal Doxorubicin in Current Therapeutic Scenarios of Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4421
Author(s):  
Francesco Schettini ◽  
Mario Giuliano ◽  
Matteo Lambertini ◽  
Rupert Bartsch ◽  
David James Pinato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Therapeutic Index ◽  
Phase Iii ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Therapeutic Algorithms ◽  
Phase Iii Trials ◽  
Standard Doxorubicin

Anthracyclines are among the most active chemotherapies (CT) in breast cancer (BC). However, cardiotoxicity is a risk and peculiar side effect that has been limiting their use in clinical practice, especially after the introduction of taxanes. Non-pegylated liposomal doxorubicin (NPLD) has been developed to optimize the toxicity profile induced by anthracyclines, while maintaining its unquestionable therapeutic index, thanks to its delivering characteristics that increase its diffusion in tumor tissues and reduce it in normal tissues. This feature allows NPLD to be safely administered beyond the standard doxorubicin maximum cumulative dose of 450–480 mg/m2. Following three pivotal first-line phase III trials in HER2-negative metastatic BC (MBC), this drug was finally approved in combination with cyclophosphamide in this specific setting. Given the increasing complexity of the therapeutic scenario of HER2-negative MBC, we have carefully revised the most updated literature on the topic and dissected the potential role of NPLD in the evolving therapeutic algorithms.

scholarly journals Incorporating CDK4/6 Inhibitors in the Treatment of Advanced Luminal Breast Cancer

Breast Care ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. 296-302 ◽  
Author(s):  
Isabel Echavarria ◽  
Yolanda Jerez ◽  
Miguel Martin ◽  
Sara López-Tarruella
Keyword(s):  
Breast Cancer ◽  
Endocrine Resistance ◽  
Safety Data ◽  
Predictive Biomarkers ◽  
Resistance Mechanisms ◽  
Phase Iii ◽  
Luminal Breast Cancer ◽  
Pivotal Phase ◽  
Phase Iii Trials ◽  
Cell Cycle Deregulation

After optimizing endocrine monotherapy modalities in the setting of advanced luminal breast cancer (BC), dual endocrine/targeted therapy combinations have been tested with positive results, and are transforming this BC subtype treatment landscape. Cell cycle deregulation is a hallmark of cancer that has become a key druggable target in hormone receptor (HR)-positive BC due to its role in endocrine resistance mechanisms. Cyclin dependent kinase (CDK)4/6 inhibitors have experienced a fast development in combination with endocrine therapy and have already been commercialized in some countries. In this review, we will summarize the development of these CDK4/6 inhibitors in luminal BC, from the preclinical data to the pivotal phase III trials that led to their approval, focusing on the efficacy and safety data for each of the treatment settings. Moreover, we will consider the challenges CDK4/6 inhibitors face in their positioning in the algorithm of treatment for advanced luminal BC and the considerations physicians should take into account when selecting these therapies for their patients. However, we are still in need of reliable predictive biomarkers in order to identify patients who will derive the greatest benefit from these drug combinations that are not exempt from toxicity.

scholarly journals Clinical Trials with Pegylated Liposomal Doxorubicin in the Treatment of Ovarian Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Carmela Pisano ◽  
Sabrina Chiara Cecere ◽  
Marilena Di Napoli ◽  
Carla Cavaliere ◽  
Rosa Tambaro ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Recurrent Ovarian Cancer ◽  
Phase Iii ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Phase Iii Trials ◽  
Platinum Refractory

Among the pharmaceutical options available for treatment of ovarian cancer, increasing attention has been progressively focused on pegylated liposomal doxorubicin (PLD), whose unique formulation prolongs the persistence of the drug in the circulation and potentiates intratumor accumulation. Pegylated liposomal doxorubicin (PLD) has become a major component in the routine management of epithelial ovarian cancer. In 1999 it was first approved for platinum-refractory ovarian cancer and then received full approval for platinum-sensitive recurrent disease in 2005. PLD remains an important therapeutic tool in the management of recurrent ovarian cancer in 2012. Recent interest in PLD/carboplatin combination therapy has been the object of phase III trials in platinum-sensitive and chemonaïve ovarian cancer patients reporting response rates, progressive-free survival, and overall survival similar to other platinum-based combinations, but with a more favorable toxicity profile and convenient dosing schedule. This paper summarizes data clarifying the role of pegylated liposomal doxorubicin (PLD) in ovarian cancer, as well as researches focusing on adding novel targeted drugs to this cytotoxic agent.

scholarly journals Pegylated Liposomal Doxorubicin in the Management of Ovarian Cancer

2010 ◽  
Vol 2 ◽  
pp. CMT.S4456
Author(s):  
Gabriella Ferrandina ◽  
Marco Petrillo ◽  
Angelo Licameli ◽  
Gilda Fuoco ◽  
Giovanni Scambia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Advanced Ovarian Cancer ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Line Treatment ◽  
Front Line ◽  
Clinical Role ◽  
High Responsiveness ◽  
Phase Iii Trials

Despite the cytoreductive efforts, and the high responsiveness to standard carboplatin/pacllitaxel front-line treatment, ovarian cancer (OvCa) remains the most lethal gynaecological malignancy with a 5-yr overall survival of only 25%–30% in advanced stage disease. Among the pharmaceutical options available for treatment of OvCa, much attention has been dedicated to pegylated liposomal doxorubicin (PLD) (Doxil® in the US; Caelyx® in Canada and Europe); this drug has a unique formulation which has entrapped conventional doxorubicin in a bilayer lipidic sphere surrounded by a polyethylene glycol layer, which prolongs the persistence of the drug in the circulation and potentiates its intratumor accumulation. These properties represent the winning resource for this drug in that sustain its very favourable toxicity profile and the safe combination with other drugs. PLD has already been approved for treatment of advanced ovarian cancer patients failing first line platinum-based treatment. Moreover, Phase III trials have been completed, which will hopefully will bring PLD to front-line treatment, and in salvage setting in combination with platinum agents. This concise review will focus on the clinical role of PLD in the management of patients with epithelial OvCa.

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