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A phase I study of personalized peptide vaccination using 14 kinds of vaccine in combination with low‐dose estramustine in HLA‐A24‐positive patients with castration‐resistant prostate cancer
Author(s) -
Noguchi Masanori,
Uemura Hirotsugu,
Naito Seiji,
Akaza Hideyuki,
Yamada Akira,
Itoh Kyogo
Publication year - 2011
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21261
Subject(s) - medicine , tolerability , adverse effect , prostate cancer , peptide vaccine , vaccination , immune system , oncology , urology , gastroenterology , cancer , immunology , antibody , epitope
BACKGROUND To evaluate the safety, tolerability, immune response, and antitumor activity of a combination of personalized peptide vaccination (PPV) and estramustine phosphate (EMP) in patients with castration‐resistant prostate cancer (CRPC). METHODS In a phase I dose‐escalation study, four peptides showing the highest levels of peptide‐specific immunoglobulin G (IgG) to 14 vaccine candidates (ITK‐1) were subcutaneously injected every week in three different dose settings (1, 3, and 5 mg per peptide) for 6 weeks with a low dose of EMP, and the patients were followed by maximum 2 years extension study either weekly or bi‐weekly six times PPV as one course with a low dose of EMP. RESULTS Fifteen patients were enrolled in the phase I study. No serious treatment‐related adverse events were observed. The most common adverse events were grade 2 skin reactions at the injection sites. The maximum acceptable dose of ITK‐1 was 8.643 mg. There were no treatment‐related systemic adverse events of grade 3 or more, and maximum tolerated dose could not be determined. Cytotoxic T lymphocyte responses measured by interferon‐γ release assay were boosted in 10 of 15 (67%) patients, and IgG responses were boosted in 7 of 15 (47%) patients. Twelve patients proceeded to the extension study, and the median survival time was 23.8 months during a median follow‐up of 23.8 months. CONCLUSIONS PPV treatment for HLA‐A24 positive patients with CRPC could be recommended for further stages of clinical trials because of its safety and the higher frequency of boosting immune responses. Prostate 77:470–479, 2011. © 2010 Wiley‐Liss, Inc.