Serum CD44 levels and response to selenium-based therapy in patients with gynecologic cancers

Abstract

2544 Background: Selenium inhibits the development of carboplatin drug resistance in a mouse ovarian cancer xenograft model and in tissue culture. Selenium inhibits the binding of ovarian cancer cells to hyaluronic acid (HA). HA is the main ligand of the CD44 receptor that is a transmembrane protein implicated in metastases and drug resistance. Based on this data we designed a phase I trial to determine MTD/DLT and any effects of selenium in carboplatin pharmacokinetics (PK) using the combination of selenious acid (Se), carboplatin (C) and paclitaxel (P) in the treatment of chemo-naive women with gynecologic malignancies. A secondary end-point was to test serum CD44 as a surrogate marker of Se effect on in vivo drug resistance. Methods: Based on the doses given on the mouse model, we administered Se intravenously (IV) on day 1, over 5 hours. On day 3, P was given at 175mg/m2 IV over 3 hours, followed by C AUC 5 (Calvert method) for 30 min every 21 days. During the first cycle C was given at an AUC of 5 an...