Enhanced therapeutic efficacy of a novel liposome-based formulation of SN-38 against human tumor models in SCID mice.

SN-38 is an active metabolite of CPT-11. The poor solubility of SN-38 in any pharmaceutically acceptable solvent and pH-dependent activity has limited its clinical use. Our objective was to evaluate an easy-to-use liposome-based formulation of SN-38 (LE-SN38) and compare the antitumor activity with its pro-drug CPT-11 against cancer cell lines and human xenograft tumor models. The cytotoxicity of LE-SN38 and CPT-11 was determined in four human cancer cell lines using the sulforhodamine B assay. The therapeutic efficacy was tested against human colon (HT-29) and breast (MX-1) xenograft tumor models in SCID mice. LE-SN38 with greater than 95% drug entrapment was found to be highly cytotoxic against four different cell lines with GI50 values of less than 0.1 microM. In the HT-29 tumor model, LE-SN38 (q x d5) at 2, 4 or 8 mg/kg resulted in 33, 81 and 91% tumor growth inhibition, respectively, compared to the drug-free liposome group. In contrast, similar dose levels of CPT-11 treatment led to only 2, 36 and 46% growth inhibition. For the MX-1 model, LE-SN38 (q x d5) regressed tumor growth by 44 and 88% at 4 and 8 mg/kg dose, respectively, whereas no regression was observed in the CPT-11-treated group. We conclude that LE-SN38 is a novel liposome-based formulation with enhanced therapeutic efficacy against human tumor models.