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

This study tested the prphylactic efficacies of doxorubincin hydrochlo ride and vincristine sulfate, encapsulated in sterically stabilised lo ng circulating liposomes, against the spontaneous development of mamma ry carcinomas in C3H/He mice. Monthly prophylactic intravenous (i.v.) injections of 6 mg/kg doses of liposome-encapsulated doxorubicin (DOX- SL) or 1 mg/kg doses of liposome-encapsulated vincristine (VIN-SL) wer e begun when retired breeding mice were 26 weeks old. Mice that develo ped a mammary carcinoma while on the monthly prophylactic protocols we re then given weekly i.v. injections of 6 mg/kg DOX-SL or 1 mg/kg VIN- SL to test the therapeutic efficacies of the drugs, and to determine w hether the tumours were susceptible or resistant to therapy. The month ly prophylactic injections reduced the incidence of first mammary carc inomas from 87/88 (99%) in untreated mice to 24/42 (57%) in DOX-SL-tre ated mice and 26/32 (81%) in VIN-SL-treated mice. Of the mice that dev eloped a mammary tumour while on the prophylactic protocols, 12 of 30 mice were cured by the weekly therapeutic use of DOX-SL, and the growt h of 18 tumours was inhibited. The weekly therapeutic use VIN-SL cured 3 of 8 mice, and inhibited the growth of five tumours. Weekly DOX-SL therapy cured 7 of 22 previously untreated mice. The mean survival of tumour-bearing mice was extended from 24 days in untreated mice to 87 days in DOX-SL-treated mice, which had not received prophylactic treat ment. Metastases were found in 29 of 54 untreated mice, and in 3 of 72 mice treated with DOX-SL and VIN-SL. Toxic side effects were limited to a transient weight loss during the weekly treatments. Drug resistan t as a result of treatments was not observed.