Phase II clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer: VENUS-PC study

Autor: Hiroaki Tanaka, Hiroto Hayashi, Haruo Iguchi, Nobuaki Suzuki, Yasunobu Koki, Tomio Ueno, Yusuke Nakamura, Tetsuya Ikemoto, Hideki Arima, Hiroyuki Furukawa, Kosei Hirakawa, Hiroaki Nagano, Masaaki Oka, Yoshitaro Shindo, Hiroto Matsui, Hiroko Takenouchi, Ryoichi Shimizu, Kazuhiro Uesugi, Kazuhiko Yoshimatsu, Toshiyoshi Fujiwara, Hidenobu Ishizaki, Michihisa Iida, Shoichi Hazama, Koichiro Sakata, Yuzo Umeda, Shigefumi Yoshino, Takashi Hatori, Mitsuo Shimada, Atsushi Aruga
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Oncology
Cancer Research
Time Factors
HLA-A24 Antigen
Kinesins
Deoxycytidine
0302 clinical medicine
Antineoplastic Combined Chemotherapy Protocols
Advanced pancreatic cancer
Aged
80 and over
General Medicine
phase II
Middle Aged
Prognosis
Treatment Outcome
030220 oncology & carcinogenesis
Original Article
Female
immunotherapy
medicine.drug
Adult
medicine.medical_specialty
Cancer Vaccines
Disease-Free Survival
03 medical and health sciences
Clinical Research
Internal medicine
Pancreatic cancer
Injection site reaction
peptide cocktail
medicine
Humans
Progression-free survival
Survival rate
Aged
Vascular Endothelial Growth Factor Receptor-1
business.industry
Cancer
Original Articles
medicine.disease
Vascular Endothelial Growth Factor Receptor-2
Gemcitabine
Pancreatic Neoplasms
Clinical trial
030104 developmental biology
CTL
Immunology
Peptide vaccine
Peptides
business
T-Lymphocytes
Cytotoxic
Zdroj: Cancer Science
ISSN: 1347-9032
Popis: We previously conducted a phase I clinical trial combining the HLA-A*2402-restricted KIF20A-derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single-armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine. Chemotherapy naïve PC patients were enrolled to evaluate primarily the 1-year survival rate, and secondarily overall survival (OS), progression free survival (PFS), response rate (RR), disease control rate (DCR) and the peptide-specific immune responses. All enrolled patients received therapy without the HLA-A information, and the HLA genotypes were used for classification of the patients. Between June 2012 and May 2013, a total of 68 patients were enrolled. No severe systemic adverse effects of Grade 3 or higher related to these three peptides were observed. The 1-year survival rates between the HLA-A*2402-matched and -unmatched groups were not significantly different. In the HLA-A*2402 matched group, patients showing peptide-specific CTL induction for KIF20A or VEGFR1 showed a better prognosis compared to those without such induction (P = 0.023, P = 0.009, respectively). In the HLA-A*2402-matched group, the patients who showed a strong injection site reaction had a better survival rate (P = 0.017) compared to those with a weak or no injection site reaction. This phase II study demonstrated that this therapeutic peptide cocktail might be effective in patients who demonstrate peptide-specific immune reactions although predictive biomarkers are needed for patient selection in its further clinical application.
Databáze: OpenAIRE
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