A phase 2 multimodality trial of docetaxel/prednisone with sunitinib followed by salvage radiation therapy (RT) in men with PSA recurrent prostate cancer (PC) after radical prostatectomy (RP).

Abstract

35 Background: In men with high grade PC and rapid PSA progression after RP, failure rates are unacceptably high despite salvage RT. Androgen deprivation therapy (ADT) is not curative in this setting and we thus evaluated a novel multi-modality approach of systemic chemotherapy and anti-angiogenic therapy prior to prostate bed salvage RT in a multicenter trial. Methods: Eligible men had a rising PSA of 0.1-3.0 ng/ml within 4 years of RP, no metastatic disease except resected positive nodes, no prior ADT, and Gleason 7-10. Men received 4 cycles of docetaxel 70 mg/m2 q3w with prednisone 5 mg bid and sunitinib 37.5 mg qd for 14/21 days each cycle. Salvage RT (66Gy/33fx) to the prostate bed started at day 100. The primary endpoint was progression-free survival at 2 years (PFS2), defined as a confirmed PSA rise above the post-RT nadir or baseline if no nadir occurred, clinical/radiographic progression, or death from date of enrollment. Safety and dose-limiting toxicities were evaluated. This was a single arm prospective open-label phase 2 trial. Results: Thirty-four men accrued in this multisite Dept. of Defense Prostate Cancer Clinical Trials Consortium trial (median age 62, 85% Caucasian, 9% African American); 24% were node positive at surgery, 47% had Gleason 8-10. Median PSA at entry was 0.54 (range 0.2-2.8) and median time since RP was 11 months. The trial was terminated prematurely due to excess dose-limiting toxicity (9 DLT events) including grade 3 events of hand-foot syndrome (n=4), neutropenic fever (n=2), AST increase (n=1), fatigue (n=1), and vomiting with diarrhea (n=1). PFS at 2 years was 48.9% (95% CI: 32.8%, 67.2%) with a median PFS of 26.2 mo (95% CI: 12.5, -). Six men (17.6%) had an undetectable PSA at 2 years. Conclusions: Sunitinib and docetaxel/prednisone followed by salvage RT resulted in excess pre-specified DLTs. However, efficacy data suggests that some men achieved durable long-term disease control with this aggressive approach. Longer-term follow-up and comparative data with salvage XRT and ADT is needed to fully understand the risks/benefits of this combined modality approach in high risk PSA-recurrent PC. Clinical trial information: NCT00734851.