Current Status of Liposomal Anthracycline Therapy in Metastatic Breast Cancer

Abstract

Doxorubicin is a mainstay for the treatment of metastatic breast cancer (MBC); however, its use is limited by toxicity, particularly cardiotoxicity. Novel drug delivery systems using liposomes have been developed to maintain the clinical utility of conventional doxorubicin while minimizing cardiotoxicity. Three liposomal anthracyclines have been developed: liposomal daunorubicin, nonpegylated liposomal doxorubicin, and pegylated liposomal doxorubicin. Liposomal daunorubicin, currently approved in the United States for the treatment of AIDS-related Kaposi sarcoma, has shown preliminary activity in MBC in a phase I trial; further investigation is ongoing. Nonpegylated liposomal doxorubicin, which is not available in the United States, has demonstrated activity similar to that of conventional doxorubicin (both as a single agent and in combinations). Pegylated liposomal doxorubicin has demonstrated activity in phase II and III trials when used alone or in combination with other chemotherapeutic agents in patients with MBC. It is currently approved in the United States and Europe for AIDS-related Kaposi sarcoma and platinum/paclitaxel-refractory ovarian carcinoma; in Europe and Canada, it is also approved as monotherapy for MBC. In addition, accumulating evidence suggests that the combination of liposomal anthracyclines (pegylated and nonpegylated) and trastuzumab is active, with acceptable toxicity. Based on these encouraging experiences, randomized clinical trials are ongoing or planned to further assess the therapeutic potential of pegylated liposomal doxorubicin as a single agent and in combination with other chemotherapeutic agents and targeted agents, such as trastuzumab, for MBC.