title: Randomized, placebo-controlled, phase III trial of sunitinib plus prednisone versus prednisone alone in progressive, metastatic, castration-resistant prostate cancer.
abstract: OBJECTIVE
  We evaluated angiogenesis-targeted sunitinib therapy in a randomized, double-blind trial of metastatic castration-resistant prostate cancer (mCRPC).
  
  
  METHODS
  Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg/d continuously or placebo. Patients also received oral prednisone 5 mg twice daily. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS). Two interim analyses were planned.
  
  
  RESULTS
  Overall, 873 patients were randomly assigned to receive sunitinib (n = 584) or placebo (n = 289). The independent data monitoring committee stopped the study for futility after the second interim analysis. After a median overall follow-up of 8.7 months, median OS was 13.1 months and 11.8 months for sunitinib and placebo, respectively (hazard ratio [HR], 0.914; 95% CI, 0.762 to 1.097; stratified log-rank test, P = .168). PFS was significantly improved in the sunitinib arm (median 5.6 v 4.1 months; HR, 0.725; 95% CI, 0.591 to 0.890; stratified log-rank test, P < .001). Toxicity and rates of discontinuations because of adverse events (AEs; 27% v 7%) were greater with sunitinib than placebo. The most common treatment-related grade 3/4 AEs were fatigue (9% v 1%), asthenia (8% v 2%), and hand-foot syndrome (7% v 0%). Frequent treatment-emergent grade 3/4 hematologic abnormalities were lymphopenia (20% v 11%), anemia (9% v 8%), and neutropenia (6% v < 1%).
  
  
  CONCLUSIONS
  The addition of sunitinib to prednisone did not improve OS compared with placebo in docetaxel-refractory mCRPC. The role of antiangiogenic therapy in mCRPC remains investigational.
authors: M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Stephane Oudard, George Pompidou European Hospital, Rene Descartes University, Paris; Nadine Houede, Institut Bergonie, Bordeaux; Tristan Maurina, CHU de Besançon, Hôpital Jean Minjoz, Besançon, France; Yen-Chuan Ou, Taichung Veterans General Hospital, Taichung, Taiwan; Lisa Sengeløv, Herlev Hospital, Herlev; Gedske Daugaard, Rigshospitalet, Copenhagen, Denmark; Fred Saad, University of Montreal, Montreal, Canada; Peter Ostler, Mount Vernon Hospital, Northwood, Middlesex; Robert Jones, Beatson West of Scotland Cancer Centre, Glasgow; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol, UK; Arnulf Stenzl, Eberhard-Karls-University Medical School, Tübingen; Juergen Gschwend, Technical University of Munich, Munich, Germany; Fredrik Laestadius and Anders Ullèn, Karolinska University Hospital, Stockholm, Sweden; Daniel Castellano, I_12 Research Institute, University Hospital 12 de Octubre, Madrid, Spain; Edna Chow Maneval, Shaw-Ling Wang, and Isan Chen, Pfizer Oncology, La Jolla, CA; and Maria Jose Lechuga and Jolanda Paolini, Pfizer Oncology, Milan, Italy.
authors: M Dror
authors: MD
authors: Michaelson
authors: Stephane
authors: S
authors: Oudard
authors: Yen-Chuan
authors: YC
authors: Ou
authors: Lisa
authors: L
authors: Sengeløv
authors: Fred
authors: F
authors: Saad
authors: Nadine
authors: N
authors: Houede
authors: Peter
authors: P
authors: Ostler
authors: Arnulf
authors: A
authors: Stenzl
authors: Gedske
authors: G
authors: Daugaard
authors: Robert
authors: R
authors: Jones
authors: Fredrik
authors: F
authors: Laestadius
authors: Anders
authors: A
authors: Ullèn
authors: Amit
authors: A
authors: Bahl
authors: Daniel
authors: D
authors: Castellano
authors: Juergen
authors: J
authors: Gschwend
authors: Tristan
authors: T
authors: Maurina
authors: Edna
authors: E
authors: Chow Maneval
authors: Shaw-Ling
authors: SL
authors: Wang
authors: Maria Jose
authors: MJ
authors: Lechuga
authors: Jolanda
authors: J
authors: Paolini
authors: Isan
authors: I
authors: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001247:Asthenia / Q000139:chemically induced; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005221:Fatigue / Q000139:chemically induced; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009919:Orchiectomy; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D000077210:Sunitinib; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007211:Indoles; D011758:Pyrroles; D043823:Taxoids; D000077143:Docetaxel; D000077210:Sunitinib; D011241:Prednisone