title: 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.
abstract: 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.
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.|Division of Urology, Department of Surgery, Duke University, Durham, NC, USA.|Duke Cancer Institute, Duke University, Durham, NC, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Armstrong
authors.affiliation: Duke Cancer Institute, Duke University, Durham, NC, USA.|Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Halabi
authors.affiliation: Duke Cancer Institute, Duke University, Durham, NC, USA.|Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
authors.forename: P
authors.initials: P
authors.lastname: Healy
authors.affiliation: Duke Cancer Institute, Duke University, Durham, NC, USA.|Department of Radiation Oncology, Duke University, Durham, NC, USA.
authors.forename: W R
authors.initials: WR
authors.lastname: Lee
authors.affiliation: Duke Cancer Institute, Duke University, Durham, NC, USA.|Department of Radiation Oncology, Duke University, Durham, NC, USA.
authors.forename: B F
authors.initials: BF
authors.lastname: Koontz
authors.affiliation: Division of Urology, Department of Surgery, Duke University, Durham, NC, USA.|Duke Cancer Institute, Duke University, Durham, NC, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Moul
authors.affiliation: Duke Cancer Institute, Duke University, Durham, NC, USA.
authors.forename: K
authors.initials: K
authors.lastname: Mundy
authors.affiliation: Duke Cancer Institute, Duke University, Durham, NC, USA.
authors.forename: P
authors.initials: P
authors.lastname: Creel
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Wood
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: K
authors.initials: K
authors.lastname: Davis
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Carducci
authors.affiliation: Rutgers Cancer Institute of NJ, New Brunswick, NJ, USA.
authors.forename: M
authors.initials: M
authors.lastname: Stein
authors.affiliation: Duke Cancer Institute, Duke University, Durham, NC, USA.
authors.forename: C
authors.initials: C
authors.lastname: Hobbs
authors.affiliation: Duke Cancer Institute, Duke University, Durham, NC, USA.
authors.forename: B
authors.initials: B
authors.lastname: Reimer
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nguyen
authors.affiliation: Duke Cancer Institute, Duke University, Durham, NC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Anand
authors.affiliation: Duke Cancer Institute, Duke University, Durham, NC, USA.
authors.forename: L
authors.initials: L
authors.lastname: Bratt
authors.affiliation: Rutgers Cancer Institute of NJ, New Brunswick, NJ, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: P T
authors.initials: PT
authors.lastname: Tran
authors.affiliation: Division of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.|Division of Urology, Department of Surgery, Duke University, Durham, NC, USA.|Duke Cancer Institute, Duke University, Durham, NC, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: George
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D000077143:Docetaxel; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D011241:Prednisone / Q000008:administration & dosage*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D011758:Pyrroles / Q000008:administration & dosage*; D011788:Quality of Life; D016879:Salvage Therapy; D000077210:Sunitinib; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D007211:Indoles; D011758:Pyrroles; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; D000077210:Sunitinib; D011241:Prednisone