Preliminary pharmacokinetics of CT-2106 (polyglutamate camptothecin) in patients with advanced malignancies

2073 Background: CT-2106 is a novel camptothecin (CPT) conjugate in which CPT is bound to a biodegradable water soluble poly-L-glutamic acid-glycine polymer. Conjugation of CPT to the polymer allows for greater stability in circulation, increased potential for exclusion from normal tissue, and enhanced permeability and retention in tumor tissue. CT-2106 has demonstrated significant anti-tumor activity in multiple human tumor cell lines in vivo, including lung and colon cancers. This study was designed to determine the pharmacokinetics of CT-2106 in patients with advanced malignancies. Methods: Patients were treated with CT-2106 as a 10 minute intravenous infusion every 21 days. Blood and urine samples were collected during treatment cycles 1 and 2. Samples were analyzed for conjugated and unconjugated CPT with validated HPLC/FD methods. Noncompartmental PK analysis of plasma concentration-time data was made by WinNonLin (Ver. 4.01). Results: Twenty-four patients have been treated. Conjugated CPT doses wer...