title: Phase II study of personalized peptide vaccination for castration-resistant prostate cancer patients who failed in docetaxel-based chemotherapy.
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.
authors.affiliation: Division of Clinical Research of the Research Center for Innovative Cancer Therapy, Kurume University School ofMedicine, 67 Asahi-machi, Kurume 830-0011, Japan. noguchi@med.kurume-u.ac.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Noguchi
authors.forename: Fukuko
authors.initials: F
authors.lastname: Moriya
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Suekane
authors.forename: Kei
authors.initials: K
authors.lastname: Matsuoka
authors.forename: Gaku
authors.initials: G
authors.lastname: Arai
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsueda
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sasada
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D019496:Cancer Vaccines / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D000077143:Docetaxel; D006801:Humans; D056724:Immunity, Humoral; D015850:Interleukin-6 / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D057285:Precision Medicine; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D043823:Taxoids / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D016207:Cytokines; D015850:Interleukin-6; D043823:Taxoids; D000077143:Docetaxel