title: A phase II trial of personalized peptide vaccination in castration-resistant prostate cancer patients: prolongation of prostate-specific antigen doubling time.
abstract: BACKGROUND
  Cancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (CRPC). However, because of delayed immune responses, its clinical benefits, besides for overall survival (OS), are not well captured by the World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Several surrogate markers for evaluation of cancer vaccine, including prostate-specific antigen doubling time (PSADT), are currently sought. The purpose of this study was to assess prospectively the PSA kinetics and immune responses, as well as the efficacy, safety, and biomarkers of personalized peptide vaccination (PPV) in progressive CRPC.
  
  
  METHODS
  One hundred patients with progressive CRPC were treated with PPV using 2-4 positive peptides from 31 candidate peptides determined by both human leukocyte antigen (HLA) class IA types and the levels of immunoglobulin G (IgG) against each peptide. The association between immune responses and PSADT as well as overall survival (OS) was studied.
  
  
  RESULTS
  PPV was safe and well tolerated in all patients with a median survival time of 18.8 months. Peptide-specific IgG and T-cell responses strongly correlated with PSADT (p < 0.0001 and p = 0.0007, respectively), which in turn showed correlation with OS (p = 0.018). Positive IgG responses and prolongation of PSADT during PPV were also significantly associated with OS (p = 0.001 and p = 0.004) by multivariate analysis.
  
  
  CONCLUSIONS
  PSADT could be an appropriate surrogate marker for evaluation of the clinical benefit of cancer vaccine. Further randomized trials are needed to confirm these results.
  
  
  BACKGROUND
  UMIN000001850.
authors.affiliation: Clinical Research Division of the Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, 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: Rei
authors.initials: R
authors.lastname: Ohnishi
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: D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D016233:Immunotherapy, Active; D007610:Kallikreins / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D057285:Precision Medicine; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D022223:Vaccines, Subunit; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen