Establishing a neoadjuvant platform for developing targeted agents: Degarelix prior to prostatectomy for patients with intermediate- and high-risk prostate cancer.

摘要

TPS5105 Background: We hypothesize that the unmet drug development needs in prostate cancer can be addressed using a standardized short exposure neoadjuvant clinical trial framework that ensures tumor tissue is available for profiling, the biomarker assays used are validated, and that trials are designed to address specific questions. This ongoing pilot study explores the response to short exposure androgen deprivation therapy (ADT) with degarelix prior to prostatectomy. The aims of the trial are to assess: (1) two time intervals to determine the maximal change in PC proliferation (Ki-67) and apoptosis rates (caspase-3) following ADT; (2) the association between PTEN status and maximal changes in proliferation and apoptosis rates in patients treated with ADT; and (3) the association between PI3K pathway (pAKT and pS6) and proliferation and apoptosis rates after treatment with ADT in relation to other markers of PC (ERG, AR and NCOA2). Methods: Thirty intermediate and high risk patients planning to undergo prostatectomy will be accrued. Two or more cores of the diagnostic biopsy must involve at least 3 mm of tissue with adenocarcinoma. Patients are randomized to receive degarelix (240 mg SC) either 4 or 7 days prior to radical prostatectomy based on the proliferation and apoptotic indexes in malignant human prostate biopsies taken 1-10 days after surgical castration which have demonstrated that maximal changes occur by day 7. (Ohlson, N., et al. Prostate 2005) Patients undergo open, laparoscopic, or robotic radical prostatectomy and are followed 6 weeks post-operatively. The first 20 patients have been successfully treated. Supported by funds from NCI P50-CA92629 SPORE in Prostate Cancer and PCF. Drug supplied by Ferring Pharmaceuticals. Clinical trial information: NCT01542021.