Modulation of the peritoneal clearance of liposomal cytosine arabinoside by blank liposomes

Summary Liposomes containing cytosine arabinoside (ara-C) release drug slowly and can be used to maintain a locally high concentration of ara-C in the peritoneal cavity for intracavitary chemotherapy. However, a significant amount of active drug does reach the systemic circulation and contributes to systemic toxicity. We have devised a novel method of decreasing toxicity and increasing intraperitoneal half-life by pretreatment with blank liposomes containing no active drug. This technique has resulted in prolongation of intraperitoneal half-life of the liposomal ara-C from 21 h to 165 h, enabling maintenance of a therapeutic drug concentration even at 11 days after initial injection. One hundred percent cures (60-day survival) were achieved with a single-dose therapy begun 1 day after i. p. implantation of 10⁶ L1210 leukemia cells.Supported in part by Public Health Service grants CA-01082, CA-35309, and CA 23100 from the National Cancer Institute, National Institute of Health, DHHS. This work was conducted in part by the Clayton Foundation for Research, California Division. Stephen B. Howell is a Clayton Foundation Investigator