SN-38, 7-ethyl-10-hydroxycamptothecin, is a biologically active metabolite of irinotecan. Its poor solubility restricted its development as an anticancer agent. We have developed an easy-to-use liposome-entrapped SN-38 (LE-SN38) and evaluated its toxicology, pharmacokinetics and antitumor efficacy profile.Toxicity and pharmacokinetics studies were conducted in CD2F1 mice and beagle dogs. Therapeutic efficacy studies were performed in murine leukemia (P388 and P388/ADR) and in a human pancreatic (Capan-1) tumor models.Multiple dose administration (i.v. x 5) of LE-SN38 indicated a maximum tolerated dose (MTD) of 5.0 and 7.5 mg/kg/day for male and female mice, respectively. The MTD of LE-SN38 in dogs was 1.2 mg/kg. The elimination half-life (t1/2) of SN-38 in mouse plasma was 6.38 h with volume of distribution (VdSS) 2.55 L/kg. In dogs, t1/2 and VdSS were 1.38-6.42 h and 1.69-5.01 L/kg; respectively. P388 tumor-bearing mice dosed with LE-SN38 at 5.5 mg/kg (i.v. x 5) showed 100% survival. LE-SN38 at 4 or 8 mg/kg (i. v. x 5) inhibited 65% and 98% tumor growth, respectively, in a human pancreatic tumor model.LE-SN38 showed a favorable pharmacokinetics profile and can be administered safely at therapeutically effective doses.