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‐γ 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  ≥ 50%. QOL outcomes were not deteriorated during the treatment. CONCLUSION 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. © 2004 Wiley‐Liss, Inc.