title: A phase I study of personalized peptide vaccination using 14 kinds of vaccine in combination with low-dose estramustine in HLA-A24-positive patients with castration-resistant prostate cancer.
abstract: BACKGROUND
  To evaluate the safety, tolerability, immune response, and antitumor activity of a combination of personalized peptide vaccination (PPV) and estramustine phosphate (EMP) in patients with castration-resistant prostate cancer (CRPC).
  
  
  METHODS
  In a phase I dose-escalation study, four peptides showing the highest levels of peptide-specific immunoglobulin G (IgG) to 14 vaccine candidates (ITK-1) were subcutaneously injected every week in three different dose settings (1, 3, and 5 mg per peptide) for 6 weeks with a low dose of EMP, and the patients were followed by maximum 2 years extension study either weekly or bi-weekly six times PPV as one course with a low dose of EMP.
  
  
  RESULTS
  Fifteen patients were enrolled in the phase I study. No serious treatment-related adverse events were observed. The most common adverse events were grade 2 skin reactions at the injection sites. The maximum acceptable dose of ITK-1 was 8.643 mg. There were no treatment-related systemic adverse events of grade 3 or more, and maximum tolerated dose could not be determined. Cytotoxic T lymphocyte responses measured by interferon-γ release assay were boosted in 10 of 15 (67%) patients, and IgG responses were boosted in 7 of 15 (47%) patients. Twelve patients proceeded to the extension study, and the median survival time was 23.8 months during a median follow-up of 23.8 months.
  
  
  CONCLUSIONS
  PPV treatment for HLA-A24 positive patients with CRPC could be recommended for further stages of clinical trials because of its safety and the higher frequency of boosting immune responses.
authors.affiliation: Department of Urology, Kurume University School of Medicine, Kurume, Japan. noguchi@med.kurume-u.ac.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Noguchi
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Uemura
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Akaza
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D003131:Combined Modality Therapy; D004306:Dose-Response Relationship, Immunologic; D004961:Estramustine / Q000008:administration & dosage*; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019496:Cancer Vaccines; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D004961:Estramustine; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen