Initial Clinical Evaluation of Pegylated-Liposomal Doxorubicin in Solid Tumors

Abstract

Recently, two liposomal anthracycline formulations have been approved by the U.S. Food and Drug Administration for clinical use (Doxil, DaunoXome).1–3 Another formulation (D-99)4 is in advanced clinical trials. As these products become available to an enlarged circle of clinicians and nurses, the need to recognize their toxicity profile becomes more urgent. When a drug is presented in a liposome formulation, the medical teams are faced with a new entity which does not fit the usual definition of a new drug. This new entity is more complex than a simple drug since it consists of a carrier, the liposome, and a drug, which may be an approved and well-known drug (e.g., doxorubicin or daunorubicin) or a newly-designed drug (e.g., annamycin5). Some clinicians tend to look at liposomal doxorubicin or liposomal daunorubicin as another drug analog among the many (epirubicin, mitoxantrone, idarubicin) that have become available in recent years. Moreover, many clinicians will refer to liposomal anthracyclines as a homogeneous group of formulations with relatively similar pharmacological and biological effects. These are dangerous oversimplifications. A learning process is required to grasp the novelty and complexity of liposome-based drug delivery systems.