A prospective, controlled phase ii study of neoadjuvant exisulind therapy before radical prostatectomy: Effect on apoptosis

Objective: To evaluate the activity of exisulind against prostate cancer (CaP) in vivo through a prospective study of neoadjuvant exisulind in patients undergoing radical prostatectomy (RP). Exisulind and its analogs have been shown to induce apoptosis in vitro in many cancer cell lines, including CaP cell lines without affecting normal human cells. Methods: Men with biopsy-proven, localized CaP (Gleason score <6) amenable to RP were offered enrollment into the trial. The treatment group (n = 44) was given oral exisulind (375-400 mg) daily for 4 weeks and then underwent RP. The control group underwent RP per routine (n = 49). The primary endpoint was change, from biopsy to prostatectomy specimens, in apoptosis biomarkers (bcl-2, Bax, par.-4, caspase 3, PTEN) between the 2 groups. Results: There were no significant effects of exisulind on biomarkers of cell death between biopsy specimen and posttreatment RP specimen. The drug was well tolerated and there were no drug-related serious adverse events or deaths. Conclusion: Exisulind is a well-tolerated drug with minimal adverse events; however, we were unable to detect any significant differences in apoptotic biomarkers among those treated with neoadjuvant exisulind compared with controls at the dose and duration tested. Future studies should consider evaluating a higher dose or longer duration to better evaluate the role exisulind may play in the treatment of men with CaP.