Phase II study of personalized peptide vaccination for castration-resistant prostate cancer patients who failed in docetaxel-based chemotherapy

Prostate. 2012 Jun 1;72(8):834-45. doi: 10.1002/pros.21485. Epub 2011 Sep 19.

Abstract

Background: Docetaxel-based chemotherapy (DBC) showed limited clinical efficacy for castration-resistant prostate cancer (CRPC) patients. To explore cancer vaccine as a new treatment modality, we conducted a phase II study of personalized peptide vaccine (PPV) for DBC-resistant CRPC patients.

Methods: Twenty DBC-resistant CRPC patients and 22 patients with no prior DBC, as a control, were treated with PPV using peptides chosen from 31 peptides in patients, respectively. Cytokines, inflammatory markers, and immune responses were measured as candidate biomarkers. DBC-resistant CRPC patients without PPV was set as a historical control for evaluation of clinical benefit of PPV.

Results: Median overall survival (OS) time from the first vaccination was 14.8 months or not reached in DBC-resistant CRPC patients and patients with no prior DBC (log-rank; P = 0.07), respectively. Median OS time from the first day of progression disease was 17.8 and 10.5 months in DBC-resistant CRPC patients receiving PPV and those with no PPV (P = 0.1656), respectively. Elevated IL-6 levels before vaccination was an unfavorable factor for OS of DBC-resistant CRPC patients (P = 0.0161, hazard ratio (HR): 0.024, 95% CI:0.001-0.499) as well as all 42 patients with PPV(P = 0.0011, HR: 0.212, 95% CI:0.068-0.661) by multivariable analysis.

Conclusions: Further clinical study of PPV is recommended for DBC-resistant CRPC patients, because of the safety and possible prolongation of MST. Control of elevated IL-6 by combined therapy may provide much better clinical outcome.

Publication types

  • Clinical Trial, Phase II
  • Controlled Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / blood
  • Cancer Vaccines / therapeutic use*
  • Cytokines / blood
  • Disease Progression
  • Docetaxel
  • Humans
  • Immunity, Humoral
  • Interleukin-6 / blood
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Orchiectomy*
  • Precision Medicine*
  • Prospective Studies
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / mortality
  • Taxoids / therapeutic use*
  • Treatment Failure
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Cancer Vaccines
  • Cytokines
  • Interleukin-6
  • Taxoids
  • Docetaxel