ABSTRACT

Doxil® Understanding Is Still OngoingResearch on Doxil® development was started in 1987. The first provisional patents were filed in 1987/1988 and the FDA approved it in 1995. Doxil has been in clinical use since 1996. Despite the long time (~28 years) that has passed and the extensive experience with its use, new information on its physicochemical and biological features is coming out. It seems that Doxil still keeps some secrets to be revealed. The new data obtained in recent years already enable a better understanding of Doxil’s mechanism

Keywords: Doxil®, liposomes, doxorubicin, delivery, anticancer, biodistribution, therapeutic efficacy, pegylated nano-liposomes, drug release rate, pharmacokinetics, tumor targeting, clinical trials, drug development

of action (MoA) and suggest combinations of Doxil with other drugs and/or biologicals, as well as use of other means that may improve its therapeutic index by improving its efficacy and/or reducing its side effects. 29.1 Historical PerspectiveI want to start this review with my recollection of a very early and cool morning in November 1995 that I will never forget. Most of the Liposome Technology Inc. (LTI) employees and I were in the big noisy storage area of LTI at 1050 Hamilton Court, Menlo Park, CA, with a lot of food, drinks, and many discussions, waiting nervously to see online the FDA’s Oncologic Drug Advisory Committee (ODAC) meeting in Washington, DC, at which a recommendation to the FDA to approve or disapprove Doxil® for Kaposi’s sarcoma indication should be given. ODAC’s session started at 08.00 AM Eastern time (05.00 AM California time). The happy end of that morning was that Doxil’s approval was recommended. Doxil is actually an abbreviation of the words “DOXorubicin In Liposomes.” Doxil® is sold in Europe as Caelyx®.