Multicentre phase II trial of combination neoadjuvant hormone therapy and weekly XXXX prior to radical prostatectomy in high risk localized @entity263 (CUOG-P01a).

@entity1 @entity137 @entity263 @entity7458 @entity5 @entity342 @entity1205
UNASSIGNED: 4635 Background: @entity1205 is active for @entity263 ( @entity263 ) and may have additive effects if combined with @entity342 ablation in hormone na  ve disease. Potential beneficial or adverse effects of combination vs sequential chemo-hormonal regimens are poorly defined. The objective of this trial was to assess the tolerability and pathologic effects (including high-throughput transcriptional and immunohistochemical bioprofiling) of 6 months of combined @entity342 ablation + @entity1205 in @entity1 with high risk localized @entity263 prior to radical prostatectomy. METHODS: In a Phase II multicentre, single arm, open-label study @entity1 with newly diagnosed previously untreated clinically localized high-risk disease received @entity342 ablation ( @entity7458 6.3 mg q 8 weeks x 3, + anti- @entity342 for 4 weeks) + weekly @entity1205 (35 mg/m2 iv weekly x 6 q 8 weeks for 3 cycles). RESULTS: 72 @entity1 with a mean age of 55 years (range 45-74) and mean serum PSA of 17.8  g/L (range 2.5-66) were enrolled at 6 sites across Canada. Baseline prognostic factors included 51% cT2 and 38% cT3; 32% Gleason 7, 32% Gleason 8, and 27% Gleason 9; PSA <10 in 44%, 10-20  g/L in 25%, and >20  g/L in 31%. Eight @entity1 discontinued study therapy for > grade 3 @entity137 (n=5), withdrawal of consent (n=1), or identification of metastatic disease (n=2). 64 @entity1 completed protocol therapy and surgery. 38 (59%) were pathological T2N0, including 2 complete responders (P-0) and 10 with residual microfoci of @entity5 . 26 (41%) were pT3, including 7 with seminal vesicle invasion (pT3c), and 4 T3N1. Positive surgical margins were identified in 17 (27%), including 5 pT2 and 12 pT3 @entity5 . CONCLUSION: Combined @entity342 ablation + weekly @entity1205 is reasonably well tolerated and results in significant pathologic responses and lower than expected positive surgical margins for this high-risk group. Tissue microarray construction and transcriptional profiling are underway to define treatment-induced changes in gene expression. [Table: see text].
