It is well tolerated at the recommended doses and possesses a broad therapeutic window [2]. Beside its use

as nutrition supplement to ameliorate cancer symptoms in patients there is incremental evidence that FWGE might exert some anticancer properties as well [1–3]. Defactinib nmr However, up to now this antitumor effect is only sparsely investigated. Thus, we screened the preclinical cytotoxic activity of FWGE as a single agent or in combination with MDV3100 manufacturer the commonly used cytostatics 5-FU, oxaliplatin or irinotecan in a large panel of human tumor cell lines to evaluate its potential antitumor properties. Human tumor cell lines or human tumor xenografts commonly serve as models for preclinical drug screening. Still, care has to be taken in the interpretation of results since their positive predictive value is limited to approximately 60-70% [18, 19]. The predictive value of preclinical cytotoxicity data could by

strengthened by the model of relative antitumor activity. It allows to estimate the potential activity of a drug in a certain tumor type by taking the preclinical IC50 value and clinically achievable peak plasma concentrations into account [20]. Only if the preclinical IC50 value is clearly below the plasma concentration that can be achieved in a patient one can assume potential clinical PP2 datasheet activity. In the present study we observed a significant antiproliferative activity of FWGE as assessed by IC50 concentrations which were in a similar range as reported by other investigators [7, 8, 21]. With a RAA ranging from approximately 1 to 24, FWGE appeared to have potential clinical activity in the broad spectrum of tumor entities used in our cell line screen. The highest activity

was found in neuroblastoma and ovarian cancer cell lines. Of particular interest for further clinical development is the relative homogeneous sensitivity of the eight colon cancer cell lines employed in this study with IC50 values ranging from 0.3-0.54 mg/ml. This prompted us to perform combination Org 27569 experiments of FWGE and chemotherapy in the colon cancer model. Overall, we could demonstrate additive to synergistic drug interaction of FWGE with irinotecan, oxaliplatin and 5-FU. These data are in line with a previous clinical report of Jakab et al.. They observed in their study with colon cancer patients an increased survival rate and reduced development of metastasis for the combination of FWGE and 5-FU-based regimens [13]. However, their clinical trial is hampered by methodological limitations and thus, data from that study are of limited significance [1]. Regimens of 5-FU and folinic acid in combination with either oxaliplatin or irinotecan are the cornerstones in the adjuvant and/or palliative treatment of colorectal cancer today [22].