Abstract #4592: Determining the toxicity and IC 50 of nano-albumin bound paclitaxel and bevacizumab in metastatic human head and neck cancer cell lines.

Introduction: Nano-albumin bound (nab) paclitaxel achieves higher intratumoral drug concentrations, with potential mechanisms including selective tumor vessel permeability, albumin-receptor-mediated transport, and increased cell permeability. The anti-vascular endothelial growth factor A (VEGF-A) antibody bevacizumab is known to enhance antitumor activity of cytotoxic drugs. Nab-paclitaxel has been recently approved for metastatic breast cancer by FDA and has shown promising results in ovarian and thoracic tumors. This study aimed at evaluating the toxic effects and determining the IC 50 of nab-paclitaxel alone and in combination with bevacizumab on metastatic human head and neck cancer cell lines. Materials and Methods: Cells were seeded in to 24 well plate with approximately 50,000 cells/500ul of media in each well plate for 8-12 hours. Cells were treated with cisplatin (64nM to 1uM) and with nab-paclitaxel alone (1.56 to 75 nM). Control wells received an equal volume of growth medium. After 72 hours, cells were dislodged by 0.2% EDTA-saline solution with trypsin, and viable cells were enumerated using the trypan blue exclusion method. Each experimental condition was tested in duplicate and reproduced in two separate experiments. The results are presented as percent of viable cells ± SD of the mean cell number in control wells. UMSCC10b and UMSCC10b/15s has been extensively characterized as cisplatin sensitive and resistant cell lines in vitro and in vivo in prior studies, respectively. We acquired these cell lines from Dr Howell. Cells were cultured at 37°C in an incubator with 5% CO 2 in humidified air using RPMI 1640 media with 10% fetal bovine serum. Tumor cells were harvested and passaged by washing with PBS, followed by 5 minutes of exposure to EDTA (0.2 mM)/trypsin diluted in PBS. Results: We examined the survival of both cell lines with cisplatin and nab-paclitaxel alone. Exposure to cisplatin resulted in 50% of UMSCC10b and UMSCC10b/15s killing at 285 nM and 1 uM, While with nab-paclitaxel IC50 was reached at 4-5 nM and 9-10 nM, respectively. Conclusion: Our data showed that nab-paclitaxel has comparable antiproliferative activity to both cisplatin resistant and cisplatin sensitive head and neck cancer cell lines. We are currently exploring the synergistic effect of nab-paclitaxel in combination with bevacizumab. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4592.