抄録
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.
| 元の言語 | English |
|---|---|
| 記事番号 | 108 |
| ジャーナル | Journal of Translational Medicine |
| 巻 | 12 |
| 発行部数 | 1 |
| DOI | |
| 出版物ステータス | Published - 2014 4 30 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
これを引用
A phase ΙI study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study). / Hazama, Shoichi; Nakamura, Yusuke; Tanaka, Hiroaki; Hirakawa, Kosei; Tahara, Ko; Shimizu, Ryoichi; Ozasa, Hiroaki; Etoh, Ryuichi; Sugiura, Fumiaki; Okuno, Kiyotaka; Furuya, Takumi; Nishimura, Taku; Sakata, Koichiro; Yoshimatsu, Kazuhiko; Takenouchi, Hiroko; Tsunedomi, Ryouichi; Inoue, Yuka; Kanekiyo, Shinsuke; Shindo, Yoshitaro; Suzuki, Nobuaki; Yoshino, Shigefumi; Shinozaki, Hirokazu; Kamiya, Akira; Furukawa, Hiroyuki; Yamanaka, Takeharu; Fujita, Tomonobu; Kawakami, Yutaka; Oka, Masaaki.
：: Journal of Translational Medicine, 巻 12, 番号 1, 108, 30.04.2014.研究成果: Article
}
TY - JOUR
T1 - A phase ΙI study of five peptides combination with oxaliplatin-based chemotherapy as a first-line therapy for advanced colorectal cancer (FXV study)
AU - Hazama, Shoichi
AU - Nakamura, Yusuke
AU - Tanaka, Hiroaki
AU - Hirakawa, Kosei
AU - Tahara, Ko
AU - Shimizu, Ryoichi
AU - Ozasa, Hiroaki
AU - Etoh, Ryuichi
AU - Sugiura, Fumiaki
AU - Okuno, Kiyotaka
AU - Furuya, Takumi
AU - Nishimura, Taku
AU - Sakata, Koichiro
AU - Yoshimatsu, Kazuhiko
AU - Takenouchi, Hiroko
AU - Tsunedomi, Ryouichi
AU - Inoue, Yuka
AU - Kanekiyo, Shinsuke
AU - Shindo, Yoshitaro
AU - Suzuki, Nobuaki
AU - Yoshino, Shigefumi
AU - Shinozaki, Hirokazu
AU - Kamiya, Akira
AU - Furukawa, Hiroyuki
AU - Yamanaka, Takeharu
AU - Fujita, Tomonobu
AU - Kawakami, Yutaka
AU - Oka, Masaaki
PY - 2014/4/30
Y1 - 2014/4/30
N2 - 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.
AB - 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.
KW - Chemotherapy
KW - Colorectal cancer
KW - FOLFOX
KW - Peptide cocktail
KW - Peptide vaccine
KW - Phase II study
UR - http://www.scopus.com/inward/record.url?scp=84899960635&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899960635&partnerID=8YFLogxK
U2 - 10.1186/1479-5876-12-108
DO - 10.1186/1479-5876-12-108
M3 - Article
C2 - 24884643
AN - SCOPUS:84899960635
VL - 12
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
SN - 1479-5876
IS - 1
M1 - 108
ER -