Multicenter, phase II clinical trial of peptide vaccination with oral chemotherapy following curative resection for stage III colorectal cancer

Kawamura,Junichiro; Sugiura,Fumiaki; Sukegawa,Yasushi; Yoshioka,Yasumasa; Hida,Jin‑Ichi; Hazama,Shoichi; Okuno,Kiyotaka

doi:10.3892/ol.2018.7905

Multicenter, phase II clinical trial of peptide vaccination with oral chemotherapy following curative resection for stage III colorectal cancer

Authors:
- Junichiro Kawamura
- Fumiaki Sugiura
- Yasushi Sukegawa
- Yasumasa Yoshioka
- Jin‑Ichi Hida
- Shoichi Hazama
- Kiyotaka Okuno
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Affiliations: Department of Surgery, Kindai University Faculty of Medicine, Osakasayama, Osaka 589‑8511, Japan, Department of Surgery, Seishukai Aiwa Hospital, Amagasaki, Hyougo 661‑0953, Japan, Institute of Immunotherapy for Cancer, Kindai University Faculty of Medicine, Osakasayama, Osaka 589‑8511, Japan, Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755‑8505, Japan
Published online on: January 29, 2018 https://doi.org/10.3892/ol.2018.7905
Pages: 4241-4247
Copyright: © Kawamura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The safety and immunological responsiveness of a peptide vaccine of ring finger protein 43 and 34‑kDa translocase of the outer mitochondrial membrane combined with uracil‑tegafur/leucovorin (UFT/LV) was previously demonstrated in metastatic colorectal cancer (CRC) in a phase I clinical trial. To clarify the survival benefit of a peptide vaccine combined with UFT/LV as adjuvant treatment, a phase II clinical trial was conducted involving patients with stage III CRC. All enrolled patients, whose human leukocyte antigen (HLA)‑A status was double‑blinded, were administered the same regime of a peptide vaccine and UFT/LV chemotherapy. The primary objective of the study was to compare relapse‑free survival (RFS) in patients with HLA‑A*2402 vs. those without HLA‑A*2402. Secondary objectives included comparisons between the two groups regarding overall survival, safety, tolerability and peptide‑specific activities of cytotoxic T lymphocytes (CTLs) as measured by the ELISPOT assay. Between December 2009 and December 2014, a total of 46 patients were enrolled to the present study. Three‑year RFS was not significantly different between HLA‑A*2402 matched and unmatched groups [67.8 vs. 73.6%, respectively; hazard ratio (HR)=1.254, 95% confidence interval (CI): 0.48‑4.63; P=0.706]. Three‑year RFS was significantly better in patients with positive CTL responses in the HLA‑A*2402 matched group compared with those without (85.7 and 33.3%, respectively; HR=0.159, 95% CI: 0.023‑0.697; P=0.011). In conclusion, vaccination‑induced immune responses combined with UFT/LV were positively associated with survival benefit in patients with HLA‑A*2402‑positive stage III CRC. Further study is required to clarify whether vaccination‑induced immune responses shortly following the initiation of therapy can predict the therapeutic effect and help develop a promising therapeutic strategy for patients with stage III CRC.

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