CHEMOPREVENTION AND THERAPY OF MOUSE MAMMARY CARCINOMAS WITH DOXORUBICIN ENCAPSULATED IN STERICALLY STABILIZED LIPOSOMES

Background. The objective of this study was to determine the ability o f doxorubicin, encapsulated in sterically stabilized liposomes (Doxil [Liposome Technology, Inc., Menlo Park, CA]), to inhibit the spontaneo us development of mammary carcinomas in mice. Methods. Monthly prophyl actic intravenous injections of 6 mg/kg doses of Doxil were started wh en retired breeding C3H/He mice were 26 weeks old. Mice that developed a mammary carcinoma were then given weekly intravenous injections of 6 mg/kg doses to determine whether the tumors were susceptible or resi stant to Doxil therapy. Results. The monthly injections reduced the in cidence of first mammary carcinomas in up to 88-week-old retired breed ing C3H/He mice from 65 of 66 (98%) in untreated mice to 22 of 47 (47% ) in treated mice. The first 15 mice that developed a mammary tumor wh ile on the prophylactic protocol were then placed on a weekly therapeu tic protocol. The therapeutic use of Doxil cured 3 of 15 mice and inhi bited the growth of 12 tumors. Drug resistance as a result of treatmen ts was not observed. The mean survival of tumor-bearing mice was exten ded from 24 days in untreated mice to 87 days in treated mice. Toxic s ide effects were limited to transient weight loss during the weekly Do xil treatments and to epidermal necrosis and dermal fibrosis due to dr ug extravasation at the sites of intravenous injections. Conclusions. The authors concluded that doxorubicin in sterically stabilized liposo mes deserves to be explored further in comparative studies with free d oxorubicin for the prophylaxis and therapy of mammary cancer.