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A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer

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Abstract

Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14–0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1–0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone.

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Abbreviations

CR:

Complete response

CT:

Computed tomography

CTL:

Cytotoxic T lymphocytes

EBV:

Epstein–Barr virus

EMP:

Estramustine phosphate

ECOG:

Eastern Cooperative Oncology Group

HLA:

Human leukocyte antigen

IFN-γ:

Interferon-γ

PBMC:

Peripheral blood mononuclear cells

HIV:

Human immunodeficiency virus

IgG:

Immunoglobulin G

PSA:

Prostate-specific antigen

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Acknowledgments

This study was supported in part by Grants-in-Aid (KAKENHI) (no.12213134 to KI), “TOSHI aria jigyo to Kurume City”, and by “High-Tech Research Center” Project for Private Universities: matching fund subsidy from Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan.

Conflict of interest statement

The authors indicated no potential conflict of interest except for Yamada and Itoh received a research grant from the Green Peptide Co., Ltd; Yamada and Itoh own stock in the Green Peptide Co.; Yamada is a part-time executive of the Green Peptide Co.

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Authors and Affiliations

  1. Department of Urology, Kurume University School of Medicine, Kurume, Japan

    Masanori Noguchi, Fukuko Moriya, Shigetaka Suekane & Kei Matsuoka

  2. Clinical Research Division, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan

    Masanori Noguchi

  3. Department of Bio-statistics, Kurume University School of Medicine, Kurume, Japan

    Tatsuyuki Kakuma

  4. Department of Urology, Kinki University School of Medicine, Sakai, Japan

    Hirotsugu Uemura

  5. Department of Urology, Faculty of Medicine, Okayama University, Okayama, Japan

    Yasutomo Nasu & Hiromi Kumon

  6. Department of Urology, Nara Medical University, Nara, Japan

    Yasuhiko Hirao

  7. Department of Immunology, Kurume University School of Medicine, Kurume, Japan

    Nobukazu Komatsu, Shigeki Shichijo, Akira Yamada & Kyogo Itoh

Authors
  1. Masanori Noguchi
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  2. Tatsuyuki Kakuma
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  3. Hirotsugu Uemura
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  4. Yasutomo Nasu
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  5. Hiromi Kumon
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  6. Yasuhiko Hirao
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  7. Fukuko Moriya
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  8. Shigetaka Suekane
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  9. Kei Matsuoka
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  10. Nobukazu Komatsu
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  11. Shigeki Shichijo
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  12. Akira Yamada
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  13. Kyogo Itoh
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Corresponding author

Correspondence to Masanori Noguchi.

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Noguchi, M., Kakuma, T., Uemura, H. et al. A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer. Cancer Immunol Immunother 59, 1001–1009 (2010). https://doi.org/10.1007/s00262-010-0822-4

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  • DOI: https://doi.org/10.1007/s00262-010-0822-4

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