Immunological evaluation of individualized peptide vaccination with a low dose of estramustine for HLA-A24+ HRPC patients.
BACKGROUND
The safety, toxicity, and immunological response of individualized peptide vaccination or human leukocyte antigen (HLA)-A24+ hormone refractory prostate cancer (HRPC) patients in combination with a low dose of estramustine were evaluated.


METHODS
Sixteen patients with HLA-A24+ HRPC were enrolled in the phase I/II study. 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 quality of life (QOL) outcomes using a self-reported patient questionnaire were also evaluated.


RESULTS
Vaccinations were well tolerated, but all patients developed grade 1 or 2 local redness and swelling at the injection site. There was no significant immunosuppression in most cases when the peptide and a half dose (280 mg/day) of estramustine were administrated. Augmentation of peptide-specific CTL precursors or peptide-specific IgG was observed in 10 of 14 or 7 of 14 patients at 12 weeks (peptide vaccination alone), and in 6 of 8 or 10 of 12 patients at 24 weeks (during the combination therapy), respectively. All 13 patients treated, with the combination therapy, showed a decrease of serum prostate-specific antigen (PSA) level from the baseline, including six patients with a serum PSA level decrease of >or=50%. QOL outcomes were not deteriorated during the treatment.


CONCLUSIONS
These results might encourage the further evaluation of the combination of peptide vaccination and a low dose of estramustine phosphate for HLA-A24+ HRPC patients.
Noguchi
Masanori
M
Department of Urology, Kurume University, Kurume, Japan. noguchi@med.kurume-u.ac.jp
Itoh
Kyogo
K
Yao
Akihisa
A
Mine
Takashi
T
Yamada
Akira
A
Obata
Yayoi
Y
Furuta
Masatoshi
M
Harada
Mamoru
M
Suekane
Shigetaka
S
Matsuoka
Kei
K
D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D004961:Estramustine / Q000008:administration & dosage*; D005500:Follow-Up Studies; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011788:Quality of Life; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage*
D018906:Antineoplastic Agents, Alkylating; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D022223:Vaccines, Subunit; D004961:Estramustine