title: 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.
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.
authors: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors: Toru
authors: T
authors: Masuzawa
authors: Yoshiyuki
authors: Y
authors: Fujiwara
authors: Kaoru
authors: K
authors: Okada
authors: Ayumu
authors: A
authors: Nakamura
authors: Shuji
authors: S
authors: Takiguchi
authors: Kiyokazu
authors: K
authors: Nakajima
authors: Hiroshi
authors: H
authors: Miyata
authors: Makoto
authors: M
authors: Yamasaki
authors: Yukinori
authors: Y
authors: Kurokawa
authors: Ryuji
authors: R
authors: Osawa
authors: Kazuyoshi
authors: K
authors: Takeda
authors: Koji
authors: K
authors: Yoshida
authors: Takuya
authors: T
authors: Tsunoda
authors: Yusuke
authors: Y
authors: Nakamura
authors: Masaki
authors: M
authors: Mori
authors: Yuichiro
authors: Y
authors: Doki
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004338:Drug Combinations; D005260:Female; D059871:HLA-A24 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000008:administration & dosage; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D005641:Tegafur / Q000008:administration & dosage; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use
chemical_list: D019496:Cancer Vaccines; D004338:Drug Combinations; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D022223:Vaccines, Subunit; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D002945:Cisplatin