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: Masanori Noguchi, Kyogo Itoh, Shigetaka Suekane, Akiko Morinaga, Aki Sukehiro, Norie Suetsugu, Kazuko Katagiri, Akira Yamada, Shinshi Noda
• Journal: The Prostate (Prostate) Vol. 60 Issue 1 Pg. 32-45 (Jun 15 2004) ISSN: 0270-4137 [Print] United States
• PMID: 15129427 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)
• Copyright: Copyright 2004 Wiley-Liss, Inc.

Chemical References

• Antineoplastic Agents, Hormonal
• Immunoglobulin G
• Vaccines, Subunit
• Estramustine
• Interferon-gamma
• Prostate-Specific Antigen

Topics

• Administration, Oral
• Aged
• Antineoplastic Agents, Hormonal (therapeutic use)
• Combined Modality Therapy
• Drug Resistance, Neoplasm
• Enzyme-Linked Immunosorbent Assay
• Estramustine (administration & dosage, therapeutic use)
• Humans
• Immunoglobulin G (analysis)
• Immunosuppression Therapy
• Interferon-gamma (analysis, biosynthesis)
• Male
• Middle Aged
• Neoplasm Metastasis
• Prostate-Specific Antigen (analysis)
• Prostatic Neoplasms (drug therapy, immunology)
• Vaccines, Subunit (administration & dosage, immunology)