title: Combination therapy of personalized peptide vaccination and low-dose estramustine phosphate for metastatic hormone refractory prostate cancer patients: an analysis of prognostic factors in the treatment.
abstract: The aim of this study was to investigate prognostic factors of patients with metastatic hormone refractory prostate cancer (HRPC) under combined administration of personalized peptide vaccination and low-dose estramustine phosphate (EMP). From February 2001 to July 2004, 58 men with metastatic HRPC received the combination therapy of personalized peptide vaccination and low-dose EMP. Conducted immune monitorings for those patients were peptide-specific cytotoxic T lymphocyte (CTL) precursor analysis by interferon-gamma production and peptide-reactive immunoglobulin G (IgG) by an enzyme-linked immunosorbent assay. Clinical responses and survival times were also evaluated. The combination therapy was well tolerated with no major adverse effects. Increased levels of CTL precursors and IgG responses to the vaccinated peptides were observed in 29 of 37 (78%) patients and in 36 of 41 (88%) patients tested, respectively. A prostate-specific antigen decline of at least 50% occurred in 24% of patients. The median survival time was 17 months (95% confidence interval, 12-25 months). Cox proportional hazards analysis showed that a low number of lymphocytes (p = 0.0075, odds ratio 2.700), a negative immunological activity response after the vaccination (p = 0.0185, odds ratio 2.658), and poor performance status (p = 0.0347, odds ratio 2.569) were independent predictors of disease death. These encouraging results show the need for further evaluation of the combination of personalized peptide vaccination and low dose of EMP for metastatic HRPC patients.
authors.affiliation: Department of Urology, 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: Takashi
authors.initials: T
authors.lastname: Mine
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Obata
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Junko
authors.initials: J
authors.lastname: Mizoguchi
authors.forename: Mamoru
authors.initials: M
authors.lastname: Harada
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Suekane
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
authors.forename: Kei
authors.initials: K
authors.lastname: Matsuoka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000917:Antibody Formation / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods / Q000706:statistics & numerical data; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D004961:Estramustine / Q000627:therapeutic use*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D016233:Immunotherapy, Active / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000628:therapy; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D010455:Peptides; D004961:Estramustine; D017430:Prostate-Specific Antigen