Prospective Evaluation of Neuromediator Dynamics in Castration-Resistant Prostate Cancer Patients During Docetaxel

Anticancer Res. 2017 Sep;37(9):5117-5124. doi: 10.21873/anticanres.11931.

Abstract

Aim: Aim of the study was to detect small cell/neuroendocrine (SCNC) transformation in metastatic castration-resistant prostate cancer (mCRPC) that is a challenging procedure. We investigated the role of neuromediator dynamics as potential evidence of SCNC in patients undergoing docetaxel therapy.

Patients and methods: A multi-institutional, prospective observational study was conducted. Patients undergoing docetaxel treatment were included. Chromogranin A (CGA), neuron-specific enolase (NSE), and pro-gastrin releasing peptide (Pro-GRP) were sequentially evaluated at predefined time points. Outcome measures were overall survival (OS), progression-free survival (PFS) and PSA nadir.

Results: Fifty-two patients were included. A general rise in CGA levels was observed. Patients with a high CGA rise (100%ULN: CGA ≥98.1ng/ml) between the 1st and 3rd cycle trended towards a decreased OS (p=0.0649) and showed a decreased PFS (p=0.0369). In multivariate analysis, continuous CGA rise correlated with PFS (p=0.0553; HR 1.136), but was not an independent predictor of OS.

Conclusion: Patients with an early high CGA rise may demonstrate a subgroup with poor outcome due to underlying SCNC transformation. Monitoring of CGA appears to be an option worth considering.

Keywords: Castration-resistant prostate cancer; chromogranin A; docetaxel; neuroendocrine transformation; neuron-specific enolase; pro-gastrin-releasing peptide.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / blood*
  • Chromogranin A / blood*
  • Docetaxel
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / blood*
  • Phosphopyruvate Hydratase / blood*
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / blood*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy
  • Recombinant Proteins / blood
  • Survival Analysis
  • Taxoids / pharmacology*
  • Taxoids / therapeutic use

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Chromogranin A
  • Peptide Fragments
  • Recombinant Proteins
  • Taxoids
  • pro-gastrin-releasing peptide (31-98)
  • Docetaxel
  • Prostate-Specific Antigen
  • Phosphopyruvate Hydratase