Results of a pilot trial of OSI-461 in patients with chronic lymphocytic leukemia

6676 Background: OSI-461 is a selective apoptotic antineoplastic drug (SAAND), a novel class of drugs that induce apoptosis by inhibiting cGMP phosphodiesterases. OSI-461 has about 100x more affinity for cGMP PDE than does exisulind, the first generation of this drug class. OSI-461 has been shown to inhibit the growth of a variety of human tumor cell lines as well as lymphocytes from CLL patients (pts). Phase-I clinical studies have also demonstrated that OSI-461 administration is well-tolerated. In this multicenter pilot study, we sought to assess the safety and activity of OSI-461 in previously untreated CLL pts. Methods: Between June 2001 and February 2002, 23 pts with progressing CLL were registered; 1 was ineligible (prior chemotherapy). Fifteen pts received OSI-461 400 mg (Group 1) and 7 received 800 mg (Group 2) PO as a split dose (200 mg [Group1] or 400 mg [Group 2]) twice daily every 28-day cycle. Patients continued to receive treatment in the absence of intolerable toxicity or disease progressio...