Liposomal doxorubicin: Doxil®

Abstract

Objective: Many cytotoxic chemotherapy agents have a narrow therapeutic index. In fact, in some patients, the onset of serious adverse effects may precede any therapeutic benefit. The use of lipo somes to target drug delivery to the site of action can improve a drug's therapeutic index by increasing its efficacy while minimizing toxicity. Liposomal doxo rubicin (Doxil®, Sequus Pharmaceuticals, Inc.)* is the first liposomal chemotherapy product to be approved in the United States. The purpose of this review is to provide a basic understanding of liposomal drug delivery, describe the unique pharmacokinetic prop erties of liposomal doxorubicin (Doxil®), and, finally, comment on this novel drug's place in therapy. Data Sources: Manual and on-line (Medline) literature searches were performed. Search terms included were the brand and generic names of the product, Kaposi's sarcoma, and liposomes. The med ical information department of Sequus Pharmaceuti cals was contacted. Study Selection: If available, controlled clinical trials with scientific merit were reviewed. Nonran domized studies, case reports, review articles, and letters to editors were considered if appropriate. Conclusions: Liposomal chemotherapy is one of many attempts to improve cytotoxic chemotherapy by maximizing tumor cell kill while minimizing pa tient adverse effects. Liposomal doxorubicin (Doxil®) is the first of such products approved for use in the United States and has a unique formulation and advantageous pharmacokinetic profile. Liposomal doxorubicin (Doxil®) is both a safe and effective agent in the treatment of advanced AIDS-related Ka posi's sarcoma. The efficacy of liposomal doxorubicin (Doxil®) in the treatment of refractory solid tumors such as breast cancer, lung cancer, colorectal cancer, renal cell cancer, ovarian cancer, and sarcoma has not been demonstrated uniformly. Limited data are avail able regarding the cardiotoxicity potential of this agent; currently no definitive conclusions can be made. Further investigation will be needed to find the ideal dose, dose schedule, and monitoring parameters for the use of liposomal doxorubicin (Doxil®) in patients with solid tumors.