title: Immunological monitoring during combination of patient-oriented peptide vaccination and estramustine phosphate in patients with metastatic hormone refractory prostate cancer.
abstract: BACKGROUND
  Additive antitumor effects could be achieved by combination of immunotherapy and cytotoxic agents with no or minimum suppression.
  
  
  METHODS
  Thirteen patients positive for human leukocyte antigen (HLA)-A24 or -A2 with metastatic hormone refractory prostate cancer (HRPC) who had failed to respond to the prior-peptide vaccination were entered in the combined peptide vaccination and estramustine phosphate. Conducted immune monitoring on those 13 patients were mainly peptide-specific cytotoxic T lymphocyte (CTL) precursor analysis by IFN-gamma productions and peptide-reactive IgG by an enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Grade 3 arrhythmia or cerebral infarction was observed in two cases, and Grade 1 or 2 dermatologic reaction at the vaccination sites was observed in all 13 cases. Eleven patients who received more than one cycle of treatment were eligible for immunological and clinical evaluation. There was no significant immunosuppression in most cases when the peptide and a half dose (280 mg/day) of estramustine were administrated, whereas severe immunosuppression was observed in the first two patients who received both the peptide and a full dose (560 mg/day) estramustine. Augmentation of peptide-specific CTL precursors or peptide-specific IgG was observed in 6 of 11 or 10 of 11 cases, respectively. Ten of 11 patients showed serum prostate-specific antigen (PSA) level decrease from the baseline including 8 patients with a serum PSA level decrease of > or =50%.
  
  
  CONCLUSIONS
  These results encouraged the further evaluation of the combination of peptide vaccination and low-dose estramustine phosphate for metastatic HRPC patients.
authors.affiliation: Department of Urology, Kurume University School of Medicine, Asahi-machi, Kurume, Japan. noguchi@med.kurume-u.ac.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Noguchi
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Suekane
authors.forename: Akiko
authors.initials: A
authors.lastname: Morinaga
authors.forename: Aki
authors.initials: A
authors.lastname: Sukehiro
authors.forename: Norie
authors.initials: N
authors.lastname: Suetsugu
authors.forename: Kazuko
authors.initials: K
authors.lastname: Katagiri
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.forename: Shinshi
authors.initials: S
authors.lastname: Noda
mesh_terms: D000284:Administration, Oral; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D004961:Estramustine / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D004961:Estramustine; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen