title: Phase II trial of bevacizumab and satraplatin in docetaxel-pretreated metastatic castrate-resistant prostate cancer.
abstract: BACKGROUND
  Satraplatin is an oral platinum compound that has demonstrated efficacy and tolerability in prostate cancer. Preclinical synergy between bevacizumab and platinum has been noted.
  
  
  METHODS
  Docetaxel-pretreated metastatic castrate-resistant prostate cancer patients with disease progression were eligible. Satraplatin 80 mg/m(2) orally on days 1 to 5, prednisone 5mg twice daily, and bevacizumab 10mg/kg on day 1, and 15 mg/kg on day 15 were administered in 35-day cycles.
  
  
  RESULTS
  Thirty one patients were enrolled. Grade 3 or 4 toxicities were pulmonary embolism in 2 patients and thrombocytopenia in 1 patient. 31% of the patients had a ≥ 30% decline in prostate-specific antigen. Median time to progression was 7.0 months (90% confidence interval [CI] 4.7-8.5mo) and median overall survival was 11.2 months (90% CI 9.1-16.4 mo). Polymorphism in the excision repair cross-complementation-1 (ERCC-1) gene was associated with time to progression (hazard ratio = 1.91). A circulating tumor cell count ≥ 5 was moderately prognostic of overall survival (hazard ratio = 1.49) as compared with CTC <5.
  
  
  CONCLUSIONS
  The combination was tolerable, and revealed promising efficacy in metastatic castrate-resistant prostate cancer. ERCC1 genotype maybe predictive of clinical benefit with platinum-based therapy in metastatic prostate cancer.
authors: Department of Oncology, Department of Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI. Electronic address: vaishamu@karmanos.org.
authors: Ulka N
authors: UN
authors: Vaishampayan
authors: Department of Oncology, Department of Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI.
authors: Joseph
authors: J
authors: Fontana
authors: Biostatistics Core, Barbara Ann Karmanos Cancer Institute, Detroit, MI.
authors: Lance K
authors: LK
authors: Heilbrun
authors: Biostatistics Core, Barbara Ann Karmanos Cancer Institute, Detroit, MI.
authors: Daryn
authors: D
authors: Smith
authors: Department of Oncology, Department of Medicine, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI.
authors: Elisabeth
authors: E
authors: Heath
authors: Clinical Trials Office, Barbara Ann Karmanos Cancer Institute, Detroit, MI.
authors: Brenda
authors: B
authors: Dickow
authors: Medical Oncology Branch, National Cancer Institute, Bethesda, MD.
authors: William D
authors: WD
authors: Figg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D004268:DNA-Binding Proteins / Q000235:genetics; D018450:Disease Progression; D004720:Endonucleases / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; C081294:satraplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D017430:Prostate-Specific Antigen
keywords: Chemotherapy; Excision repair polymorphism; Phase II clinical trial; Prostate cancer