Investigator-initiated pilot study of sunitinib malate in patients with newly diagnosed prostate cancer prior to prostatectomy: A trial of the DoD/PCF Prostate Cancer Clinical Trials Consortium.

4664 Background: Sunitinib malate (Sutent, Pfizer) is an oral multi-targeted tyrosine kinase inhibitor of VEGF/PDGF receptors that may function in part to inhibit prostate tumor growth via anti-angiogenic mechanisms. METHODS: We conducted a multi-site study of sunitinib in patients with newly diagnosed, clinically localized prostate cancer prior to prostatectomy. After meeting eligibility requirements (intermediate to high risk, localized prostate cancer, adequate laboratory parameters, no prior treatment for prostate cancer), subjects received sunitinib 50mg PO for 28 days followed by a 1 week washout period followed by either radical retropubic or robot-assisted prostatectomy. Pathologic specimens (pretreatment biopsies and prostatectomy specimens) were evaluated for apoptotic (TUNEL) and proliferation (Ki-67) indices, microvessel density (MVD) and gene expression patterns. RESULTS: 31 subjects were enrolled (median age 60 yrs; ECOG=0, biopsy Gleason 3+4=7). Data analysis is complete for 28 subjects. Most common toxicities (>30%) were diarrhea, fatigue, hypertension, mucositis, neutropenia, taste alterations, and thrombocytopenia. Most common grade 3-4 toxicities (> 5%) were hypertension, increased AST/ALT, and neutropenia. Median PSA decline was 13.6% (range -32% to 80%). Median change in Ki-67 was -34% (lower quartile -64% upper quartile +1.3%); median change in TUNEL was 4.5% (lower quartile -76%, upper quartile +286%); and median change in MVD (CD31) was +22% (lower quartile -23%, upper quartile +110%). Gene expression analysis is ongoing. CONCLUSIONS: Sunitinib given in the pre-prostastectomy setting appears safe and tolerable with a similar toxicity profile seen in patients with advanced cancer. Changes in proliferation and apoptosis suggest a treatment effect, while increases in MVD suggest a possible rebound effect off of sunitinib.

Duke Scholars

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics

Author Andrew John Armstrong Medicine, Medical Oncology

Author Judd Wendell Moul Urology