Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer

Toru Masuzawa, Yoshiyuki Fujiwara, Kaoru Okada, Ayumu Nakamura, Shuji Takiguchi, Kiyokazu Nakajima, Hiroshi Miyata, Makoto Yamasaki, Yukinori Kurokawa, Ryuji Osawa, Kazuyoshi Takeda, Koji Yoshida, Takuya Tsunoda, Yusuke Nakamura, Masaki Mori, Yuichiro Doki

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Abstract

The aim of this study was to evaluate the safety and efficacy of vaccination with human leukocyte antigen (HLA)-A24-restricted human vascular endothelial growth factor receptor 1 (VEGFR1)-1084 and VEGFR2-169 combined with chemotherapy in patients with advanced gastric cancer. HLA-A*2402-positive patients with advanced or recurrent adenocarcinoma of the stomach were vaccinated with VEGFR1-1084 and VEGFR2-169 combined with S-1 and cisplatin. The study included 22 patients (median age 60.5 years) who received at least one cycle of the combination therapy. No severe adverse effects caused by the vaccine therapy were observed except for an inflammatory reaction at the site of injection in 6 patients. Twelve patients (55%) showed partial response and 10 had stable disease after two cycles of the combination therapy. The disease control rate (partial response and stable disease) was 100% after two cycles. The median time to progression was 9.6 months and median overall survival was 14.2 months. VEGFR1-1084-specific cytotoxic T lymphocyte (CTL) response was induced in 18 (82%) of the 22 patients and VEGFR2-169-specific CTL response was induced in 18 (82%) of the 22 patients. Patients showing CTL response to VEGFR2-169 peptide had significantly better prognosis than those without, as demonstrated by the overall survival (OS) and time to progression (TTP) (OS, p=0.028, TTP, p=0.006). The combination therapy was well tolerated and highly effective in advanced or recurrent gastric cancer. Substantial specific CTL for both peptides was frequently induced even under chemotherapy. Thus, cancer vaccination combined with standard chemotherapy warrants further analysis as a promising strategy for the treatment of advanced cancer.

Original languageEnglish
Pages (from-to)1297-1304
Number of pages8
JournalInternational journal of oncology
Volume41
Issue number4
DOIs
Publication statusPublished - Oct 1 2012

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Vascular Endothelial Growth Factor Receptor-1
Subunit Vaccines
Cisplatin
Stomach Neoplasms
Cytotoxic T-Lymphocytes
HLA Antigens
Drug Therapy
Survival
Vaccination
Active Immunotherapy
human KDR protein
Therapeutics
Neoplasms
Stomach
Adenocarcinoma
Safety
Peptides
Injections

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer. / Masuzawa, Toru; Fujiwara, Yoshiyuki; Okada, Kaoru; Nakamura, Ayumu; Takiguchi, Shuji; Nakajima, Kiyokazu; Miyata, Hiroshi; Yamasaki, Makoto; Kurokawa, Yukinori; Osawa, Ryuji; Takeda, Kazuyoshi; Yoshida, Koji; Tsunoda, Takuya; Nakamura, Yusuke; Mori, Masaki; Doki, Yuichiro.

In: International journal of oncology, Vol. 41, No. 4, 01.10.2012, p. 1297-1304.

Research output: Contribution to journalArticle

Masuzawa, T, Fujiwara, Y, Okada, K, Nakamura, A, Takiguchi, S, Nakajima, K, Miyata, H, Yamasaki, M, Kurokawa, Y, Osawa, R, Takeda, K, Yoshida, K, Tsunoda, T, Nakamura, Y, Mori, M & Doki, Y 2012, 'Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer', International journal of oncology, vol. 41, no. 4, pp. 1297-1304. https://doi.org/10.3892/ijo.2012.1573
Masuzawa, Toru ; Fujiwara, Yoshiyuki ; Okada, Kaoru ; Nakamura, Ayumu ; Takiguchi, Shuji ; Nakajima, Kiyokazu ; Miyata, Hiroshi ; Yamasaki, Makoto ; Kurokawa, Yukinori ; Osawa, Ryuji ; Takeda, Kazuyoshi ; Yoshida, Koji ; Tsunoda, Takuya ; Nakamura, Yusuke ; Mori, Masaki ; Doki, Yuichiro. / Phase I/II study of S-1 plus cisplatin combined with peptide vaccines for human vascular endothelial growth factor receptor 1 and 2 in patients with advanced gastric cancer. In: International journal of oncology. 2012 ; Vol. 41, No. 4. pp. 1297-1304.
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abstract = "The aim of this study was to evaluate the safety and efficacy of vaccination with human leukocyte antigen (HLA)-A24-restricted human vascular endothelial growth factor receptor 1 (VEGFR1)-1084 and VEGFR2-169 combined with chemotherapy in patients with advanced gastric cancer. HLA-A*2402-positive patients with advanced or recurrent adenocarcinoma of the stomach were vaccinated with VEGFR1-1084 and VEGFR2-169 combined with S-1 and cisplatin. The study included 22 patients (median age 60.5 years) who received at least one cycle of the combination therapy. No severe adverse effects caused by the vaccine therapy were observed except for an inflammatory reaction at the site of injection in 6 patients. Twelve patients (55{\%}) showed partial response and 10 had stable disease after two cycles of the combination therapy. The disease control rate (partial response and stable disease) was 100{\%} after two cycles. The median time to progression was 9.6 months and median overall survival was 14.2 months. VEGFR1-1084-specific cytotoxic T lymphocyte (CTL) response was induced in 18 (82{\%}) of the 22 patients and VEGFR2-169-specific CTL response was induced in 18 (82{\%}) of the 22 patients. Patients showing CTL response to VEGFR2-169 peptide had significantly better prognosis than those without, as demonstrated by the overall survival (OS) and time to progression (TTP) (OS, p=0.028, TTP, p=0.006). The combination therapy was well tolerated and highly effective in advanced or recurrent gastric cancer. Substantial specific CTL for both peptides was frequently induced even under chemotherapy. Thus, cancer vaccination combined with standard chemotherapy warrants further analysis as a promising strategy for the treatment of advanced cancer.",
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AU - Fujiwara, Yoshiyuki

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AU - Nakamura, Ayumu

AU - Takiguchi, Shuji

AU - Nakajima, Kiyokazu

AU - Miyata, Hiroshi

AU - Yamasaki, Makoto

AU - Kurokawa, Yukinori

AU - Osawa, Ryuji

AU - Takeda, Kazuyoshi

AU - Yoshida, Koji

AU - Tsunoda, Takuya

AU - Nakamura, Yusuke

AU - Mori, Masaki

AU - Doki, Yuichiro

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N2 - The aim of this study was to evaluate the safety and efficacy of vaccination with human leukocyte antigen (HLA)-A24-restricted human vascular endothelial growth factor receptor 1 (VEGFR1)-1084 and VEGFR2-169 combined with chemotherapy in patients with advanced gastric cancer. HLA-A*2402-positive patients with advanced or recurrent adenocarcinoma of the stomach were vaccinated with VEGFR1-1084 and VEGFR2-169 combined with S-1 and cisplatin. The study included 22 patients (median age 60.5 years) who received at least one cycle of the combination therapy. No severe adverse effects caused by the vaccine therapy were observed except for an inflammatory reaction at the site of injection in 6 patients. Twelve patients (55%) showed partial response and 10 had stable disease after two cycles of the combination therapy. The disease control rate (partial response and stable disease) was 100% after two cycles. The median time to progression was 9.6 months and median overall survival was 14.2 months. VEGFR1-1084-specific cytotoxic T lymphocyte (CTL) response was induced in 18 (82%) of the 22 patients and VEGFR2-169-specific CTL response was induced in 18 (82%) of the 22 patients. Patients showing CTL response to VEGFR2-169 peptide had significantly better prognosis than those without, as demonstrated by the overall survival (OS) and time to progression (TTP) (OS, p=0.028, TTP, p=0.006). The combination therapy was well tolerated and highly effective in advanced or recurrent gastric cancer. Substantial specific CTL for both peptides was frequently induced even under chemotherapy. Thus, cancer vaccination combined with standard chemotherapy warrants further analysis as a promising strategy for the treatment of advanced cancer.

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