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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2014

Open Access 01-12-2014 | Research

A phase ΙI study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study)

Authors: Shoichi Hazama, Yusuke Nakamura, Hiroaki Tanaka, Kosei Hirakawa, Ko Tahara, Ryoichi Shimizu, Hiroaki Ozasa, Ryuichi Etoh, Fumiaki Sugiura, Kiyotaka Okuno, Takumi Furuya, Taku Nishimura, Koichiro Sakata, Kazuhiko Yoshimatsu, Hiroko Takenouchi, Ryouichi Tsunedomi, Yuka Inoue, Shinsuke Kanekiyo, Yoshitaro Shindo, Nobuaki Suzuki, Shigefumi Yoshino, Hirokazu Shinozaki, Akira Kamiya, Hiroyuki Furukawa, Takeharu Yamanaka, Tomonobu Fujita, Yutaka Kawakami, Masaaki Oka

Published in: Journal of Translational Medicine | Issue 1/2014

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Abstract

Background

We previously conducted a phase I trial for advanced colorectal cancer (CRC) using five HLA-A*2402-restricted peptides, three derived from oncoantigens and two from vascular endothelial growth factor (VEGF) receptors, and confirmed safety and immunological responses. To evaluate clinical benefits of cancer vaccination treatment, we conducted a phase II trial using the same peptides in combination with oxaliplatin-based chemotherapy as a first-line therapy.

Methods

The primary objective of the study was the response rates (RR). Progression free survival (PFS), overall survival (OS), and immunological parameters were evaluated as secondary objective. The planned sample size was more than 40 patients for both HLA2402-matched and -unmatched groups. All patients received a cocktail of five peptides (3 mg each) mixed with 1.5 ml of IFA which was subcutaneously administered weekly for the first 12 weeks followed by biweekly administration. Presence or absence of the HLA-A*2402 genotype were used for classification of patients into two groups.

Results

Between February 2009 and November 2012, ninety-six chemotherapy naïve CRC patients were enrolled under the masking of their HLA-A status. Ninety-three patients received mFOLFOX6 and three received XELOX. Bevacizumab was added in five patients. RR was 62.0% and 60.9% in the HLA-A*2402-matched and -unmatched groups, respectively (p = 0.910). The median OS was 20.7 months in the HLA-A*2402-matched group and 24.0 months in the unmatched group (log-rank, p = 0.489). In subgroup with a neutrophil/lymphocyte ratio (NLR) of < 3.0, patients in the HLA-matched group did not survive significantly longer than those in the unmatched group (log-rank, p = 0.289) but showed a delayed response.

Conclusions

Although no significance was observed for planned statistical efficacy endpoints, a delayed response was observed in subgroup with a NLR of < 3.0. Biomarkers such as NLR might be useful for selecting patients with a better treatment outcome by the vaccination.

Trial registration

Trial registration: UMIN000001791.
Appendix
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Metadata
Title
A phase ΙI study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study)
Authors
Shoichi Hazama
Yusuke Nakamura
Hiroaki Tanaka
Kosei Hirakawa
Ko Tahara
Ryoichi Shimizu
Hiroaki Ozasa
Ryuichi Etoh
Fumiaki Sugiura
Kiyotaka Okuno
Takumi Furuya
Taku Nishimura
Koichiro Sakata
Kazuhiko Yoshimatsu
Hiroko Takenouchi
Ryouichi Tsunedomi
Yuka Inoue
Shinsuke Kanekiyo
Yoshitaro Shindo
Nobuaki Suzuki
Shigefumi Yoshino
Hirokazu Shinozaki
Akira Kamiya
Hiroyuki Furukawa
Takeharu Yamanaka
Tomonobu Fujita
Yutaka Kawakami
Masaaki Oka
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2014
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-12-108

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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