DOXORUBICIN ENCAPSULATED IN STERICALLY STABILIZED LIPOSOMES IS SUPERIOR TO FREE DRUG OR DRUG-CONTAINING CONVENTIONAL LIPOSOMES AT SUPPRESSING GROWTH AND METASTASES OF HUMAN LUNG-TUMOR XENOGRAFTS

Liposomes containing polyethylene glycol-derivatized phospholipids are able to evade the reticuloendothelial system and thereby remain in ci rculation for prolonged periods, We report here that doxorubicin encap sulated in these sterically stabilized liposomes (S-DOX) suppresses th e growth of established human lung tumor xenografts in severe combined immunodeficient (SCID) mice and inhibits the spontaneous metastases o f these tumors, The enhanced therapeutic efficacy of S-DOX compared to free doxorubicin was demonstrated in two independent human/mouse mode ls, In the first model, S-DOX inhibited the growth of a human non-smal l cell lung tumor xenograft established orthotopically in the lungs of SCID mice. Treatment of these mice with S-DOX, but not with free drug , suppressed the growth of the tumor in the lung, prevented metastasis from the lung, and enhanced survival percentage. In another model, th e human lung tumor is engrafted into the gonadal fat pad of SCID mice. Human tumor xenografts grow floridly in this site of engraftment, and the tumor spreads from this primary site into the peritoneal cavity a nd subsequently reaches the liver and lung. In this model, free drug s uppressed the growth of the primary tumor but had no effect upon the s ubsequent spread of the tumor into the peritoneal cavity, liver, and l ung. In contrast, treatment of the tumor-hearing mice with S-DOX (but not with doxorubicin in conventional liposomes) suppressed the tumor s pread to the peritoneal cavity, completely arrested metastasis to the liver and lung, and suppressed the growth of the primary tumor xenogra ft. This report provides the first evidence that antitumor drugs deliv ered by sterically stabilized liposomes can arrest the metastasis of h uman tumor xenografts.