Abstract 4420: ABI-013: A novel nanoparticle albumin-bound (nab) docetaxel analog with superior antitumor activity over docetaxel

Abstract

Abstract Background: Docetaxel-based chemotherapy is currently used to treat patients with a variety of tumors. A critical challenge has been to improve its chemotherapeutic levels without systemic toxicity. We developed ABI-013, a novel analog of docetaxel (Taxotere®) as a solvent (polysorbate 80/ethanol)-free, nanoparticle albumin-bound 70-nm (nab) form with improved stability in vivo as a tumor-targeting chemotherapeutic agent. In this study, we evaluated the comparative antitumor activity of ABI-013 versus Taxotere® in human tumor xenografts. Methods: Subcutaneous human breast (MDA-MB-231), colon (HT29 and HCT-116), and lung (H358) tumors were grown in athymic nude mice and treated intravenously (IV) with ABI-013 (15, 30, 60, 90, 120 or 150 mg/kg) or Taxotere (MTD of 15 mg/kg) on a q4dx3 schedule. Evaluations of anti-tumor activity were based on the number of partial and complete regressions, the median number of days for tumors in each group to reach one tumor mass doubling (T-C) or the percentage tumor growth inhibition (%TGI). Results: Significant dose-dependent TGI was observed with complete or partial tumor regressions in all xenograft models treated with ABI-013. In the MDA-MB-231 breast tumor model, ABI-013 effectively delayed the tumor growth with T-C values of 83.1, 80.7, and >84.8 days at dosages of 120, 90, and 60 mg/kg, respectively, with >96% TGI compared to vehicle control (P < 0.0001 vs. saline). In contrast, Taxotere delayed the tumor growth with a T-C value of 49.5 days and decreased tumor growth by 88% (P < 0.0001 vs. saline). In the HT 29 colon tumor model, Taxotere revealed dose-limiting toxicity with a 27% body weight loss (BWL) despite 86 to 91% TGI (P < 0.01 vs. saline). In contrast, ABI-013 (90 mg/kg) caused complete tumor regression with a maximum BWL of 19% (P < 0.0001 vs. saline). Treatment with Taxotere delayed the growth of HCT-116 colon tumor with a T-C value of 14.9 days with a maximum BWL of 21%. In contrast, complete tumor regression was achieved in 40% of ABI-013-treated mice. In the H358 human non-small cell lung cancer model, unlike Taxotere, ABI-013 (60 mg/kg) caused partial tumor regression with minimal toxicity. Conclusion: ABI-013, a solvent-free nanoparticle albumin-bound 70-nm particle form of a novel docetaxel analog, had superior antitumor activity in human breast, colorectal, and lung cancer xenograft models compared with equitoxic doses of solvent-based formulation of docetaxel. The nab form of the novel docetaxel analog shows promise in cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4420.