Abstract 2539: Antitumor effects of oral paclitaxel DHP107 on gastric cancer xenografts

Oral paclitaxel DHP107 (Daehwa, Seoul Korea), an antineoplastic agent, is effectively absorbed through the gastrointestinal tract via the lipid uptake mechanism, which is currently under clinical investigation. Oral capecitabine generates 5-fluorouracil (5-FU) by thymidine phosphorylase, preferentially in tumor tissue. Taxanes, such as paclitaxel and docetaxel, have the ability to up-regulate levels of thymidine phosphorylase which show the its increased activity in tumors compared with that of normal tissue. Accordingly, combination treatment using taxanes with capecitabine is effective in several tumors, especially in gastric cancer. In this study, we investigated the antitumor effect of DHP107 combined with capecitabine and compared the effects of DHP107 and Taxol in gastric cancer xenografts. DHP107 in combination with capecitabine dramatically inhibited tumor growth without additive toxicity compared with each agent used alone in gastric xenografts. The expression of the level of thymidine phosphorylase in tumor was markedly increased four hours after treatment with DHP107. The apoptotic effects, assessed using TUNEL and soft agar colony-formation assay on xenograft tumors, were greater with combined treatment than with either agent used alone. The antitumor effects of DHP107 were similar to those of Taxol in gastric cancer xenografts. These data indicate that DHP107 combined with capecitabine had enhanced antitumor effects in human gastric tumor xenografts and that DHP107 had antitumor effects in gastric cancer models, both of which provide support for future clinical trials of DHP107. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2539. doi:10.1158/1538-7445.AM2011-2539