Free and Liposomal Doxorubicin Treatment of Intraperitoneal Colon 26 Tumor: Therapeutic and Pharmacologic Studies

Abstract

Intraperitoneal (i.p.) chemotherapy is being investigated as an adjunct to surgery to kill residual cancer cells, inhibit cancer cell seeding, local recurrence, and metastases for ovarian, gastric, and colon cancers. In this report, the therapeutic effects of Doxorubicin (Dox) and liposome-entrapped Dox (Dox-Lip) against i.p. mouse colon 26 (C26) tumor were compared. It was found that Dox-Lip was less toxic than Dox after i.p. administration in non-tumor bearing animals. I.P. Dox and Dox-Lip significantly inhibited the growth of C26 tumor when the treatment was initiated 1 day after tumor cell inoculation, but both administration forms were ineffective against well-established (8-day) tumors. Multiple dose schedules did not improve the therapeutic response. Dox-Lip was not therapeutically superior to Dox at equal doses or at approximately equi-toxic doses. In addition, the relative retention of Dox and Dox-Lip in the peritoneal cavity and their plasma pharmacokinetics were investigated. It was found that Dox levels in the peritoneal cavity were maintained for longer periods after i.p. Dox-Lip was administered. However, the results show that maintenance of elevated drug levels in the peritoneal cavity does not necessarily lead to increased therapeutic effects.