ELISIDEPSIN Antineoplastic Agent

Elisidepsin (Irvalec(R), PM02734) is a depsipeptide produced by chemical synthesis and chosen for development as an antineoplastic agent based on its in vitro activity against human solid tumor cell lines, in vivo activity in hollow fibers and xenografted human tumors, as well as its acceptable preclinical toxicology profile. Elisidepsin causes a typical necrotic cell death and induces profound alterations in tumor cell morphology. The compound is currently under clinical evaluation in four phase I trials: two as a single-agent iv. infusion and evaluating three every-3-week (q3wk) schedules: 30 min, 3 h and 24 h; two in combination with erlotinib; and another in combination with carboplatin or gemcitabine. On the basis of the previous phase I/II experience with a related compound, kahalalide F, an ongoing phase II clinical trial is currently evaluating elisidepsin over 30 min q3wk in patients with squamous non-small cell lung cancer. Furthermore, the finding of one complete response and cases of long-lasting stable disease in phase! trials has prompted a phase Ib/II trial in patients with advanced/metastatic esophageal, gastric or gastroesophageal junction cancer.