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Docetaxel is a poorly water-soluble semi-synthetic taxane analog commonly used in the treatment of non-small cell lung, prostate, and breast cancer. Because of it is poor water-solubility it is formulated with co-solvents that can potentially contribute to treatment-related adverse events such as hypersensitivity reactions. Current taxane formulations often complicate drug delivery and can alter both pharmacokinetic and toxicity profiles. Azaya Therapeutics, Inc. has encapsulated docetaxel (ATI-1123) utilizing a novel proprietary nanotechnology-based platform Protein Stabilized Liposomes (PSLTM) that avoids these major formulation issues, potentially resulting in a safer and more efficacious drug delivery system.

To evaluate and compare activity of ATI-1123 to standard docetaxel, we performed single agent efficacy studies in several human tumor xenograft models representing prostate (PC-3), pancreatic (PANC-1), and non-small cell lung (H460) malignancies. Standard docetaxel was tested intravenously (IV) at its maximum tolerated dose (MTD) and ½ MTD (13 and 6.5 mg/kg) once every other day for three treatments (Q2Dx3) while ATI-1123 was administered IV at 12.5 and 25 mg/kg on an identical schedule. Significant endpoints for these studies included tumor growth inhibition (TGI), partial or complete tumor regression, and agent toxicity as measured by weight loss and deaths. In these studies, standard docetaxel produced dose-dependent tumor growth inhibition and statistically significant (p<0.05) activity at 13 mg/kg. Comparable TGI results were reported in groups dosed with ATI-1123 at 12.5 mg/kg, suggesting liposomal encapsulation had no negative effect on drug activity. Treatment with ATI-1123 at 25 mg/kg resulted in statistically significant (p<0.05) tumor growth inhibition and partial tumor regressions in 8/9 (PC-3) and 5/7 (PANC-1) animals, which was not seen in groups dosed with standard docetaxel; weight loss was comparable with standard docetaxel at its MTD.

These results support further investigation of ATI-1123 as an alternative to the current clinical docetaxel formulation. Additional studies evaluating enhanced benefits of ATI-1123 including alterations in drug distribution, tolerability, and anti-tumor efficacy are underway as well as efforts to encapsulate other hydrophobic anticancer agents using the PSLTM platform.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA