Liposomal Anthracyclines in Metastatic Breast Cancer: Clinical Update

Anthracyclines are a mainstay of therapy for patients with metastatic breast cancer. However, their use has been limited by associated toxicities, including myelosuppression, alopecia, nausea and vomiting, stomatitis, and most importantly, cardiotoxicity. Liposomal anthracyclines were developed to increase the therapeutic index of conventional anthracyclines by maintaining antitumor efficacy while improving the safety profile. There are currently three liposomal formulations: liposomal daunorubicin, liposomal doxorubicin (D-99), and pegylated liposomal doxorubicin. Only one phase I study has been conducted with liposomal daunorubicin for metastatic breast cancer. Liposomal doxorubicin has shown comparable efficacy with conventional doxorubicin and less toxicity. Pegylated liposomal doxorubicin is the most widely studied of the liposomal anthracyclines and has demonstrated similar efficacy to conventional doxorubicin and a better safety profile, including significantly less cardiotoxicity, in patients with metastatic breast cancer. Pegylated liposomal doxorubicin has shown efficacy as a single agent and in combination with many agents, including cyclophosphamide, paclitaxel, docetaxel, and gemcitabine, with response rates ranging from 33%-75%. Growing evidence supports the use of pegylated liposomal doxorubicin as first-line treatment for patients with metastatic breast cancer, owing to its antitumor activity in both anthracycline-naïve patients and in patients with previous anthracycline exposure.