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 of doxorubicin, encapsulated in sterically stabilized liposomes (Doxil [Liposome Technology, Inc., Menlo Park, CA]), to inhibit the spontaneous development of mammary carcinomas in mice.

METHODS

Monthly prophylactic intravenous injections of 6 mg/kg doses of Doxil were started when 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 resistant to Doxil therapy.

RESULTS

The monthly injections reduced the incidence of first mammary carcinomas in up to 88-week-old retired breeding 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 while on the prophylactic protocol were then placed on a weekly therapeutic protocol. The therapeutic use of Doxil cured 3 of 15 mice and inhibited the growth of 12 tumors. Drug resistance as a result of treatments was not observed. The mean survival of tumor-bearing mice was extended from 24 days in untreated mice to 87 days in treated mice. Toxic side effects were limited to transient weight loss during the weekly Doxil treatments and to epidermal necrosis and dermal fibrosis due to drug extravasation at the sites of intravenous injections.

CONCLUSIONS

The authors concluded that doxorubicin in sterically stabilized liposomes deserves to be explored further in comparative studies with free doxorubicin for the prophylaxis and therapy of mammary cancer.