ABSTRACT
II. Therapeutic Effects ................................................................................................... 150 A. Human Carcinoma Heterografts ......................................................................... 150
1. Prostatic Carcinoma ....................................................................................... 150 2. Ovarian Carcinoma ........................................................................................ 151
B. Mouse Mammary Carcinoma Isografts .............................................................. 154 1. Implanted Tumors .......................................................................................... 154 2. Spontaneous Metastases ................................................................................. 157 3. Combination Therapy .................................................................................... 159
C. Primary Mouse Mammary Carcinomas ............................................................. 163 1. Prophylaxis ..................................................................................................... 165 2. Therapy ........................................................................................................... 166
References ........................................................................................................................... 171
A number of studies in animal tumor models have found that the therapeutic effects of several anticancer drugs will be enhanced and prolonged, and toxic side effects reduced, when the drugs are encapsulated in liposomes. 1-4 The improved therapeutic effect is thought to be due to the slow release of drugs from liposomes.5 The effectiveness of drugs in conventional liposomes is limited, however, by their rapid uptake by the cells of the reticuloendothelial system (RES),6•7 reducing the amount of drug that may reach the tumor.7 The uptake of liposomes by the RES is decreased and their circulation time increased, by the covalent attachment of polyethylene glycol to the lipid bilayers (sterically stabilized liposomes, a formulation characteristic named Stealth*).8•9 The increased accumulation of sterically stabilized liposomes in tumors outside RES organs10 is supported by observations, using standard and electron microscopy, of the accumulation of sterically stabilized liposomes containing colloidal gold in the extravascular spaces of tumor stroma. 11 The therapeutic efficacy of doxorubicin against several mouse mammary carcinomas was shown to be increased by encapsulating the drug in sterically stabilized liposomes, Doxil *, in comparisons with the drug in conventional liposomes, or free in saline. 12 From the intratumor location, a drug would be slowly released from the liposomes and would maintain the optimum local intracellular and extracellular cytotoxic levels, 13 for prolonged periods.
