Multicenter, phase II clinical trial of peptide vaccination with oral chemotherapy following curative resection for stage III colorectal cancer
- Junichiro Kawamura
- Fumiaki Sugiura
- Yasushi Sukegawa
- Yasumasa Yoshioka
- Jin‑Ichi Hida
- Shoichi Hazama
- Kiyotaka Okuno
Published online on: January 29, 2018
Copyright: © Kawamura et al.
This is an open access article distributed under the terms of Creative Commons Attribution License.
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.