Back to Search Start Over

A randomized phase II trial of personalized peptide vaccine with low dose cyclophosphamide in biliary tract cancer.

Authors :
Shirahama, Takahisa
Muroya, Daisuke
Matsueda, Satoko
Yamada, Akira
Shichijo, Shigeki
Naito, Masayasu
Yamashita, Takuto
Sakamoto, Shinjiro
Okuda, Koji
Itoh, Kyogo
Sasada, Tetsuro
Yutani, Shigeru
Source :
Cancer Science; May2017, Vol. 108 Issue 5, p838-845, 8p
Publication Year :
2017

Abstract

Since the prognosis of advanced biliary tract cancer ( aBTC) still remains very poor, new therapeutic approaches, including immunotherapies, need to be developed. In the current study, we conducted an open-label randomized phase II study to test whether low dose cyclophosphamide ( CPA) could improve antigen-specific immune responses and clinical efficacy of personalized peptide vaccination ( PPV) in 49 previously treated aBTC patients. Patients with aBTC refractory to at least one regimen of chemotherapies were randomly assigned to receive PPV with low dose CPA (100 mg/day for 7 days before vaccination) ( PPV/ CPA, n = 24) or PPV alone ( n = 25). A maximum of four HLA-matched peptides were selected based on the pre-existing peptide-specific IgG responses, followed by subcutaneous administration. T cell responses to the vaccinated peptides in the PPV/ CPA arm tended to be greater than those in the PPV alone arm. The PPV/ CPA arm showed significantly better progression-free survival (median time: 6.1 vs 2.9 months; hazard ratio ( HR): 0.427; P = 0.008) and overall survival (median time: 12.1 vs 5.9 months; HR: 0.376; P = 0.004), compared to the PPV alone arm. The PPV alone arm, but not the PPV/ CPA arm, showed significant increase in plasma IL-6 after vaccinations, which might be associated with inhibition of antigen-specific T cell responses. These results suggested that combined treatment with low dose CPA could provide clinical benefits in aBTC patients under PPV, possibly through prevention of IL-6-mediated immune suppression. Further clinical studies would be recommended to clarify the clinical efficacy of PPV/ CPA in aBTC patients. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
13479032
Volume :
108
Issue :
5
Database :
Complementary Index
Journal :
Cancer Science
Publication Type :
Academic Journal
Accession number :
123299247
Full Text :
https://doi.org/10.1111/cas.13193