Anthracyclines Strike Back: Rediscovering Non-Pegylated Liposomal Doxorubicin in Current Therapeutic Scenarios of Breast Cancer
Francesco Schettini, Mario Giuliano, Matteo Lambertini, Rupert Bartsch, David J. Pinato, Concetta Elisa Onesti, Nadia Harbeck, Diana Lüftner, Sylvie Rottey, Peter A. van Dam, Khalil Zaman, Giorgio Mustacchi, Joseph Gligorov, Ahmad Awada, Mario Campone, Hans Wildiers, Alessandra Gennari, Vivianne C. G. Tjan‐Heijnen, Javier Cortés, Mariavittoria Locci, Ida Paris, Lucia Del Mastro, Sabino De Placido, Miguel Martín, Guy Jérusalem, Sergio Venturini, Giuseppe Curigliano, Daniele Generali
Abstract
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.