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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 Xenografts¹

Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263

Liposomes containing polyethylene glycol-derivatized phospholipids are able to evade the reticuloendothelial system and thereby remain in circulation for prolonged periods. We report here that doxorubicin encapsulated in these sterically stabilized liposomes (S-DOX) suppresses the growth of established human lung tumor xenografts in severe combined immunodeficient (SCID) mice and inhibits the spontaneous metastases of these tumors. The enhanced therapeutic efficacy of S-DOX compared to free doxorubicin was demonstrated in two independent human/mouse models. In the first model, S-DOX inhibited the growth of a human non-small 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, the 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 and subsequently reaches the liver and lung. In this model, free drug suppressed the growth of the primary tumor but had no effect upon the subsequent spread of the tumor into the peritoneal cavity, liver, and lung. In contrast, treatment of the tumor-bearing mice with S-DOX (but not with doxorubicin in conventional liposomes) suppressed the tumor spread to the peritoneal cavity, completely arrested metastasis to the liver and lung, and suppressed the growth of the primary tumor xenograft. This report provides the first evidence that antitumor drugs delivered by sterically stabilized liposomes can arrest the metastasis of human tumor xenografts.

¹ This work was supported in part by Grants CA54491 and CA57974 awarded by the National Cancer Institute, United States Department of Health, Education and Welfare.

² Current affiliation: SEQUUS Pharmaceuticals, Inc., Menlo Park, California 94025.

³ To whom requests for reprints should be addressed, at Department of Molecular Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263.

Received 12/ 1/95. Accepted 6/12/96.

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