Abstract
Simple SummaryAnthracyclines are among the most active chemotherapies in breast cancer (BC). However, they can cause structural and cumulative dose-related cardiac damage; hence, they require careful administration after preliminary functional cardiac assessment and subsequent monitoring, along with a limitation in the cumulative dose delivered. Non-pegylated liposomal doxorubicin (NPLD) has been precisely developed to optimize the doxorubicin toxicity profile, while retaining its therapeutic efficacy, thanks to a reduced diffusion in normal tissues with preserved drug penetrance into cancer sites. This has allowed administration of NPLD beyond a conventional doxorubicin maximum cumulative dose, as well as in patients with cardiac comorbilities or anthracycline pretreatment. At present, NPLD is approved in Europe and Canada in combination with cyclophosphamide as the first line of metastatic HER2-negative BC. However, given the increasing complexity of the therapeutic scenario in this setting, we have carefully revised the most updated literature on the topic and dissected the potential role of NPLD in the evolving therapeutic algorithms.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.
Highlights
Anthracyclines are among the most active chemotherapeutic agents in breast cancer (BC), along with taxanes
It is important to take into consideration that the evaluation of LVEF with multiplegated arteriography (MUGA) or echocardiography (ECHO) is considered to be mandatory before the start of treatment and at each additional administration of Non-pegylated liposomal doxorubicin (NPLD) once a patient exceeds a lifetime cumulative anthracycline dose of 550 mg/m2 or whenever cardiomyopathy is suspected [63]
NPLD + cyclophosphamide is currently approved as a first-line CT for HER2-negative metastatic BC (MBC)
Summary
Anthracyclines are among the most active chemotherapeutic agents in breast cancer (BC), along with taxanes. The pegylated liposomal form of doxorubicin (PLD) is currently approved as a single agent in metastatic BC (MBC) at high risk of cardiotoxicity and shows some differences in the pharmacokinetic and pharmacodynamic profiles as compared with the non-pegylated liposomal formulation [10]. These distinctive features are at the basis of a more delayed administration schedule and some differences in the toxicity profile. Within this paper, we will focus on non-pegylated liposomal doxorubicin (NPLD), with the aim of dissecting its differences with conventional anthracyclines, and highlighting its relevance and optimal positioning in the current therapeutic algorithms
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