Efficacy and cardiovascular safety of liposomal doxorubicin: a systematic review and meta-analysis of randomized trials

Anthracyclines can cause dose-dependent cardiotoxicity that may be irreversible. To minimize cardiotoxic effects, substituting doxorubicin for liposomal doxorubicin (LD) has been explored as a cardioprotective strategy. To describe randomized clinical trials (RCTs) comparing the efficacy and safety of LD with other anthracycline-based regimens. We conducted a systematic review and meta-analysis of RCTs comparing LD with other anthracycline-based regimens, using data from Medline, Embase, Emcare, the Cochrane Central Register, and LILACS. Twelve studies including 3027 patients with breast cancer (6), multiple myeloma (2), lymphoma (2), sarcoma (1), and acute lymphocytic leukemia (1) were included. Most participants (86%) were women with breast cancer. Nine studies compared LD with conventional doxorubicin and three with epirubicin. Overall, the risk of bias was classified as "some concerns". Follow-up ranged from 24–72 months – the median follow-up time among the studies was 37 months. There was a reduction in heart failure (HF) incidence in the LD group compared to the control (RR 0.32, 95%CI 0.18–0.55). A significant decrease in left ventricular ejection fraction (LVEF), as defined by each study´s criteria, was less frequent in the LD group compared to other anthracycline-based therapies (RR 0.39, 95%CI 0.30–0.51). All-cause mortality (RR 0.98, 95%CI 0.90–1.07) and tumor response (RR 0.99, 95%CI 0.93–1.05) did not differ between the groups. LD use was associated with a decrease in the occurrence of HF compared to other anthracycline-based therapies, with no worse cancer outcomes. A significant decrease in LVEF was also less frequent in the LD group; however, no difference was found in cardiovascular mortality. Efficacy and Cardiovascular Safety of Liposomal Doxorubicin. We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 12. We identified randomized controlled trials in which the use of liposomal doxorubicin was compared to another anthracycline-containing regimen. In 12 studies, including 3027 patients with breast cancer (6), multiple myeloma (2), lymphoma (2), sarcoma (1), and acute lymphocytic leukemia (1), there was a reduction in heart failure incidence in the liposomal doxorubicin group compared to the control, with no worse cancer outcomes.