Liposomes as carriers of antitumor agents: Toward a clinical reality

For several years, liposomes have been explored as carriers of antitumor agents. Liposomes can be administered intravenously to carry lipid-soluble drugs, to improve drug stability, to target organs with fenestrated capillaries, to achieve an intravascular slow drug-release system, and to reduce drug levels in certain organs sensitive to toxicity. They also have significant potential for local therapy when administered subcutaneously or intraperitoneally. The preclinical development of liposome-entrapped antitumor agents has been, in general, slowed by cumbersome formulation problems. However, during the last few years, new drug loading techniques and a better selection of the drugs for liposome entrapment have resulted in pharmaceutically acceptable liposomal formulations or antitumor agents. Three preparations have been approved by the Federal Drug Administration, two containing doxorubicin, and the other a new lipophilic cisplatin analogue [cis-bis-neodecanoato-trans-R,R-1,2-diamino-cyclohexane platinum (II)]. In preclinical studies, these preparations were shown to be less toxic than the parent compounds and more active in models of liver micrometastases. Clinical Phase I and II studies with these formulations are now in progress. Although liposomal antitumor agents have no established role in the anticancer armamentarium at this stage, the information available suggests that they may improve the therapeutic index or broaden the applications of available antitumor agents and possibly act as carriers for newly designed liposome-dependent antitumor agents.