Phase II trial of bevacizumab and satraplatin in docetaxel-pretreated metastatic castrate-resistant prostate cancer

Urol Oncol. 2014 Jan;32(1):31.e25-33. doi: 10.1016/j.urolonc.2012.11.017. Epub 2013 Feb 21.

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.

Keywords: Chemotherapy; Excision repair polymorphism; Phase II clinical trial; Prostate cancer.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • DNA-Binding Proteins / genetics
  • Disease Progression
  • Endonucleases / genetics
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating
  • Organoplatinum Compounds / administration & dosage*
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • DNA-Binding Proteins
  • Organoplatinum Compounds
  • Bevacizumab
  • satraplatin
  • ERCC1 protein, human
  • Endonucleases
  • Prostate-Specific Antigen