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

BACKGROUND - In men with high Gleason PC and rapid PSA progression after surgery, failure rates remain unacceptably high despite salvage radiation. We explored a novel multimodality approach of docetaxel with anti-angiogenic therapy before salvage radiotherapy (RT).

METHODS - This was a phase 2 single-arm prospective open-label trial with historic controls. Eligible men had a rising PSA of 0. 1-3. 0 ng ml(-1) within 4 years of radical prostatectomy, no metastases except resected nodal disease, no prior androgen-deprivation therapy (ADT) and Gleason 7-10. Men received four cycles of docetaxel 70 mg m(-2) every 3 weeks with low dose prednisone and sunitinib 37. 5 mg daily for 14/21 days each cycle, with no ADT. Salvage prostate bed RT (66 Gy) started at day 100. The primary end point was progression-free survival (PFS) rate at 24 months. Safety data, quality of life (QOL) and dose-limiting toxicities (DLTs) were measured over time.

RESULTS - Thirty-four men accrued in this multi-institutional clinical trial: 24% of men were node positive, 47% were Gleason 8-10, median PSA at entry was 0. 54. The trial was terminated prematurely owing to excess DLTs (nine) including grade 3 hand-foot syndrome (n=4), neutropenic fever (n=2), AST increase (n=1), fatigue (n=1) and vomiting with diarrhea (n=1). PFS rate at 24 months was 51% (95% CI: 33, 67%) with a median PFS of 26. 2 months (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. Although nearly half of the men experienced durable disease control, efficacy was not greater than expected with radiation alone. The use of the intermediate end point of PFS in this salvage setting permitted an early decision on further development of this combination. Prostate Cancer and Prostatic Diseases advance online publication, 12 January 2016; doi:10. 1038/pcan. 2015. 59.

Prostate cancer and prostatic diseases. 2016 Jan 12 [Epub ahead of print]

A J Armstrong, S Halabi, P Healy, W R Lee, B F Koontz, J W Moul, K Mundy, P Creel, S Wood, K Davis, M A Carducci, M Stein, C Hobbs, B Reimer, M Nguyen, M Anand, L Bratt, S Kim, P T Tran, D J George, Department of Defense Prostate Cancer Clinical Trials Consortium (DOD PCCTC)

Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA. , Duke Cancer Institute, Duke University, Durham, NC, USA. , Duke Cancer Institute, Duke University, Durham, NC, USA. , Duke Cancer Institute, Duke University, Durham, NC, USA. , Duke Cancer Institute, Duke University, Durham, NC, USA. , Division of Urology, Department of Surgery, Duke University, Durham, NC, USA. , Duke Cancer Institute, Duke University, Durham, NC, USA. , Duke Cancer Institute, Duke University, Durham, NC, USA. , Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA. , Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA. , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. , Rutgers Cancer Institute of NJ, New Brunswick, NJ, USA. , Duke Cancer Institute, Duke University, Durham, NC, USA. , Duke Cancer Institute, Duke University, Durham, NC, USA. , Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA. , Duke Cancer Institute, Duke University, Durham, NC, USA. , Duke Cancer Institute, Duke University, Durham, NC, USA. , Rutgers Cancer Institute of NJ, New Brunswick, NJ, USA. , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. , Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.

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