Immunological monitoring during combination of patient-oriented peptide vaccination and estramustine phosphate in patients with metastatic hormone refractory prostate cancer

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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‐γ 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 ≥50%. CONCLUSIONS These results encouraged the further evaluation of the combination of peptide vaccination and low‐dose estramustine phosphate for metastatic HRPC patients.