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Article

Phase I clinical trial of a peptide vaccine combined with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer

  • Authors:
    • Norimasa Matsushita
    • Atsushi Aruga
    • Yuji Inoue
    • Yoshihito Kotera
    • Kazuyoshi Takeda
    • Masakazu Yamamoto
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan, Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
  • Pages: 951-959
    |
    Published online on: January 10, 2013
       https://doi.org/10.3892/or.2013.2231
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Abstract

Recently, analysis of tumor antigens using micro­arrays has revealed upregulation of cancer-testis antigens RNF43 and TOMM34 and vascular endothelial growth factor receptors VEGFR1 and VEGFR2 in colorectal cancer. A phase I clinical trial of peptide vaccine therapy together with oral anticancer drugs was conducted to treat advanced colorectal cancer using synthesized peptides of these tumor antigens in order to confirm the safety, immunogenicity and activity of this treatment. The subjects were patients with a human leukocyte antigen (HLA) type of A2402 who had inoperable colorectal cancer but had failed to respond to or were unable to undergo standard chemotherapy. Four peptides (RNF43, TOMM34, VEGFR1 and VEGFR2) were emulsified with incomplete Freund's adjuvant (Montanide), and the resulting solution was administered subcutaneously once a week. Patients received the oral anticancer drug tegafur-uracil plus leucovorin for four weeks continuously as part of one course followed by one week of rest. The primary endpoint of the trial was observation of adverse events as determined by the NCI-CTCAE criteria, and the secondary endpoints were the size of the tumor and the number of cytotoxic T lymphocytes (CTLs) in the peripheral blood after treatment. Vaccine therapy was administered 148 times to 10 patients from July 2008 to December 2009. The adverse events were grade 1 redness and induration, a grade 2 skin ulcer at the vaccination site and grade 1 pyrexia. All patients tolerated treatment. Tumor imaging revealed that after 1 course of treatment 1 patient had partial response (PR), 7 had stable disease (SD) and 2 had progressive disease. A CTL assay of 10 patients revealed an increase in peptide-specific CTLs in patients with PR and SD, and the clinical responses of those patients were observed. Kaplan‑Meier analysis indicated that patients who had a strong CTL reaction had a tendency to have longer progression‑free survival and overall survival.
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Copy and paste a formatted citation
Spandidos Publications style
Matsushita N, Aruga A, Inoue Y, Kotera Y, Takeda K and Yamamoto M: Phase I clinical trial of a peptide vaccine combined with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer. Oncol Rep 29: 951-959, 2013.
APA
Matsushita, N., Aruga, A., Inoue, Y., Kotera, Y., Takeda, K., & Yamamoto, M. (2013). Phase I clinical trial of a peptide vaccine combined with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer. Oncology Reports, 29, 951-959. https://doi.org/10.3892/or.2013.2231
MLA
Matsushita, N., Aruga, A., Inoue, Y., Kotera, Y., Takeda, K., Yamamoto, M."Phase I clinical trial of a peptide vaccine combined with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer". Oncology Reports 29.3 (2013): 951-959.
Chicago
Matsushita, N., Aruga, A., Inoue, Y., Kotera, Y., Takeda, K., Yamamoto, M."Phase I clinical trial of a peptide vaccine combined with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer". Oncology Reports 29, no. 3 (2013): 951-959. https://doi.org/10.3892/or.2013.2231
Copy and paste a formatted citation
x
Spandidos Publications style
Matsushita N, Aruga A, Inoue Y, Kotera Y, Takeda K and Yamamoto M: Phase I clinical trial of a peptide vaccine combined with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer. Oncol Rep 29: 951-959, 2013.
APA
Matsushita, N., Aruga, A., Inoue, Y., Kotera, Y., Takeda, K., & Yamamoto, M. (2013). Phase I clinical trial of a peptide vaccine combined with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer. Oncology Reports, 29, 951-959. https://doi.org/10.3892/or.2013.2231
MLA
Matsushita, N., Aruga, A., Inoue, Y., Kotera, Y., Takeda, K., Yamamoto, M."Phase I clinical trial of a peptide vaccine combined with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer". Oncology Reports 29.3 (2013): 951-959.
Chicago
Matsushita, N., Aruga, A., Inoue, Y., Kotera, Y., Takeda, K., Yamamoto, M."Phase I clinical trial of a peptide vaccine combined with tegafur-uracil plus leucovorin for treatment of advanced or recurrent colorectal cancer". Oncology Reports 29, no. 3 (2013): 951-959. https://doi.org/10.3892/or.2013.2231
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