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 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.

Randomized Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Patients With Platinum-Resistant Ovarian Cancer

2007 ◽  
Vol 25 (19) ◽  
pp. 2811-2818 ◽  
Author(s):  
David G. Mutch ◽  
Mauro Orlando ◽  
Tiana Goss ◽  
Michael G. Teneriello ◽  
Alan N. Gordon ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Single Agent ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Therapeutic Index ◽  
Phase Iii ◽  
End Points ◽  
Platinum Resistant ◽  
Significant Difference

Purpose Ovarian cancer (OC) patients experiencing progressive disease (PD) within 6 months of platinum-based therapy in the primary setting are considered platinum resistant (Pt-R). Currently, pegylated liposomal doxorubicin (PLD) is a standard of care for treatment of recurrent Pt-R disease. On the basis of promising phase II results, gemcitabine was compared with PLD for efficacy and safety in taxane-pretreated Pt-R OC patients. Patients and Methods Patients (n = 195) with Pt-R OC were randomly assigned to either gemcitabine 1,000 mg/m2 (days 1 and 8; every 21 days) or PLD 50 mg/m2 (day 1; every 28 days) until PD or undue toxicity. Optional cross-over therapy was allowed at PD or at withdrawal because of toxicity. Primary end point was progression-free survival (PFS). Additional end points included tumor response, time to treatment failure, survival, and quality of life. Results In the gemcitabine and PLD groups, median PFS was 3.6 v 3.1 months; median overall survival was 12.7 v 13.5 months; overall response rate (ORR) was 6.1% v 8.3%; and in the subset of patients with measurable disease, ORR was 9.2% v 11.7%, respectively. None of the efficacy end points showed a statistically significant difference between treatment groups. The PLD group experienced significantly more hand-foot syndrome and mucositis; the gemcitabine group experienced significantly more constipation, nausea/vomiting, fatigue, and neutropenia but not febrile neutropenia. Conclusion Although this was not designed as an equivalency study, gemcitabine and PLD seem to have a comparable therapeutic index in this population of Pt-R taxane-pretreated OC patients. Single-agent gemcitabine may be an acceptable alternative to PLD for patients with Pt-R OC.

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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