Abstract 4587: Combined administration of Voluven® 10% and anti-cancer drugs increases anti-tumor efficacy

Abstract

Abstract Background: Standard-of-care anti-cancer drugs exhibit anti-tumor activity but typically display dose-limiting toxicities in patients. The aim of the current studies was to investigate, whether a combined approach consisting of a pre-treatment with the hydroxyethyl starch solution Voluven® 10% and a subsequent treatment with suboptimal doses of selected anti-cancer drugs improves the anti-cancer efficacy in human tumor xenograft models in mice. Materials and methods: Female NMRI nu/nu mice bearing subcutaneous xenografts of the human lung squamous cell carcinoma LXFE 397 were treated i.v. with 20 ml/kg Voluven® 10% followed by a p.o. treatment with 100 mg/kg capecitabine 1 hour later on days 0, 4, 7, 11, and 14. In a separate study, female NMRI nu/nu mice bearing subcutaneous xenografts of the human head-and-neck carcinoma HNXF 1842 were treated i.v. with 20 ml/kg Voluven® 10% followed by an i.v. treatment with 10 mg/kg paclitaxel 1 hour later on days 0, 7 and 14. In both studies, dosing started on the day of randomization (day 0) when animals carried tumors of appropriate size (50-250 mm3). Saline (20 ml/kg) served as negative control and the anti-cancer drug alone as reference. From the day of first dosing, the tumor growth and body weight were monitored over a time period of 14 days in the lung carcinoma study and 18 days in the head-and-neck carcinoma study. Results: In mice bearing human lung squamous cell carcinoma xenografts, the median relative tumor volume increased approximately 19-fold in the saline group during the 14 days observation time, whereas the reference drug capecitabine moderately inhibited the tumor growth. Combining capecitabine treatment with a Voluven® 10% pre-treatment caused a much stronger inhibitory effect on tumor growth as evidenced by an 8.5-fold median relative tumor volume increase in contrast to a 15.2-fold increase in the reference group (capecitabine). In mice bearing human head-and-neck carcinoma xenografts, the median relative tumor volume of the saline group increased 12.1-fold during the observation period of 18 days. The treatment with paclitaxel caused a tumor growth reduction resulting in a 7.1-fold increase of the median relative tumor volume. This effect was further enhanced by the pre-treatment with Voluven® 10% which resulted in a 4-fold median relative tumor volume increase over 18 days. The combination of Voluven® 10% with capecitabine or paclitaxel did not increase toxicity as demonstrated by the body weight development. Conclusion: We showed for the first time that the pre-treatment with Voluven® 10% 1 hour prior to the administration of the anti-cancer drugs capecitabine or paclitaxel is useful to improve their efficacy in tumor xenograft models in mice. The enhancement of anti-cancer drug effectiveness might allow reducing the dosage of cytotoxic anti-cancer drugs and therefore minimizing unwanted side effects. Citation Format: Silke Baasner, Corinna Lupp, Stefanie Honndorf, Johannes Hermle, Martin Westphal. Combined administration of Voluven® 10% and anti-cancer drugs increases anti-tumor efficacy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4587. doi:10.1158/1538-7445.AM2014-4587