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Pancreatic Neoplasms: HELP
Articles by Makoto Ueno
Based on 47 articles published since 2010
(Why 47 articles?)
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Between 2010 and 2020, Makoto Ueno wrote the following 47 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review A review of changes to and clinical implications of the eighth TNM classification of hepatobiliary and pancreatic cancers. 2019

Ueno, Makoto / Morizane, Chigusa / Ikeda, Masafumi / Okusaka, Takuji / Ishii, Hiroshi / Furuse, Junji. ·Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Chuo-ku, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. · Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan. · Department of Medical Oncology, Kyorin University Faculty of Medicine, Japan. ·Jpn J Clin Oncol · Pubmed #31822900.

ABSTRACT: Hepatobiliary and pancreatic cancers have poor outcomes. Clinical staging is useful for predicting survival and selecting treatment options. The 8th edition of tumor-node metastasis (TNM) was published in 2016 and came into effect from 2018. Regarding liver cancer (hepatocellular carcinoma), tumour size and vascular invasion were more emphasized adding numbers. Tumour size was included for intrahepatic cholangiocarcinoma. T2 for gallbladder cancer was divided into two categories based on the side of invasion, and lymph node metastasis was classified according to the number of lymph nodes, not the site. The N category for perihilar cholangiocarcinoma was changed to the same as that for gallbladder cancer (total number of regional lymph nodes). The depth of tumour invasion using cut-off values of 5 and 12 mm was adopted as the T category for distal cholangiocarcinoma. The N category was also changed (the total number of regional lymph nodes). Regarding cancer of the ampulla of Vater, the T category was classified in more detail and the N category was also changed to the total number of regional lymph nodes. T1 for pancreatic cancer was separated into T1 subcategories (T1a, T1b and T1c) based on cut-off values of 5 and 10 mm. T1-T3 were classified with cut-off values of ≤2 cm, >2 to 4 cm and >4 cm. Furthermore, the N category was changed to the total number of regional lymph nodes. Although there are limitations due to treatment decisions only being based on imaging interpretation, this classification predicts the prognosis of patients more accurately than the previous edition.

2 Review Familial pancreatic cancer: Concept, management and issues. 2017

Matsubayashi, Hiroyuki / Takaori, Kyoichi / Morizane, Chigusa / Maguchi, Hiroyuki / Mizuma, Masamichi / Takahashi, Hideaki / Wada, Keita / Hosoi, Hiroko / Yachida, Shinichi / Suzuki, Masami / Usui, Risa / Furukawa, Toru / Furuse, Junji / Sato, Takamitsu / Ueno, Makoto / Kiyozumi, Yoshimi / Hijioka, Susumu / Mizuno, Nobumasa / Terashima, Takeshi / Mizumoto, Masaki / Kodama, Yuzo / Torishima, Masako / Kawaguchi, Takahisa / Ashida, Reiko / Kitano, Masayuki / Hanada, Keiji / Furukawa, Masayuki / Kawabe, Ken / Majima, Yoshiyuki / Shimosegawa, Toru. ·Hiroyuki Matsubayashi, Division of Endoscopy, Shizuoka Cancer Center, Shizuoka 411-8777, Japan. ·World J Gastroenterol · Pubmed #28246467.

ABSTRACT: Familial pancreatic cancer (FPC) is broadly defined as two first-degree-relatives with pancreatic cancer (PC) and accounts for 4%-10% of PC. Several genetic syndromes, including Peutz-Jeghers syndrome, hereditary pancreatitis, hereditary breast-ovarian cancer syndrome (HBOC), Lynch syndrome, and familial adenomatous polyposis (FAP), also have increased risks of PC, but the narrowest definition of FPC excludes these known syndromes. When compared with other familial tumors, proven genetic alterations are limited to a small proportion (< 20%) and the familial aggregation is usually modest. However, an ethnic deviation (Ashkenazi Jewish > Caucasian) and a younger onset are common also in FPC. In European countries, "anticipation" is reported in FPC families, as with other hereditary syndromes; a trend toward younger age and worse prognosis is recognized in the late years. The resected pancreases of FPC kindred often show multiple pancreatic intraepithelial neoplasia (PanIN) foci, with various K-

3 Review An overview of genetic polymorphisms and pancreatic cancer risk in molecular epidemiologic studies. 2011

Lin, Yingsong / Yagyu, Kiyoko / Egawa, Naoto / Ueno, Makoto / Mori, Mitsuru / Nakao, Haruhisa / Ishii, Hiroshi / Nakamura, Kozue / Wakai, Kenji / Hosono, Satoyo / Tamakoshi, Akiko / Kikuchi, Shogo. ·Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Japan. ·J Epidemiol · Pubmed #21071884.

ABSTRACT: BACKGROUND: Although pancreatic cancer has been extensively studied, few risk factors have been identified, and no validated biomarkers or screening tools exist for early detection in asymptomatic individuals. We present a broad overview of molecular epidemiologic studies that have addressed the relationship between pancreatic cancer risk and genetic polymorphisms in several candidate genes and suggest avenues for future research. METHODS: A comprehensive literature search was performed using the PubMed database. RESULTS: Overall, individual polymorphisms did not seem to confer great susceptibility to pancreatic cancer; however, interactions of polymorphisms in carcinogen-metabolizing genes, DNA repair genes, and folate-metabolizing genes with smoking, diet, and obesity were shown in some studies. The major problem with these studies is that, due to small sample sizes, they lack sufficient statistical power to explore gene-gene or gene-environment interactions. Another important challenge is that the measurement of environmental influence needs to be improved to better define gene-environment interaction. It is noteworthy that 2 recent genome-wide association studies of pancreatic cancer have reported that variants in ABO blood type and in 3 other chromosomal regions are associated with risk for this cancer, thus providing new insight into pancreatic cancer etiology. CONCLUSIONS: As is the case in other complex diseases, common, low-risk variants in different genes may act collectively to confer susceptibility to pancreatic cancer in individuals with repeated environmental exposures, such as smoking and red meat intake. Clarification of gene-gene and gene-environmental interaction is therefore indispensable for future studies. To address these issues, a rigorously designed molecular epidemiologic study with a large sample is desirable.

4 Clinical Trial Phase I/II Study: Experience with the Late Onset of Acute Pancreatitis after the Start of Chemotherapy with Gemcitabine Plus nab-Paclitaxel for Metastatic Pancreatic Cancer. 2019

Ueno, Makoto / Nagashima, Fumio / Ueno, Hideki / Ikeda, Masafumi / Ohkawa, Shinichi / Mizuno, Nobumasa / Ioka, Tatsuya / Omuro, Yasushi / Nakajima, Takako Eguchi / Furuse, Junji. ·Division of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Japan. · Department of Medical Oncology, Kyorin University Faculty of Medicine, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, Japan. · Department of Cancer Survey and Gastrointestinal Oncology, Osaka International Cancer Institute, Japan. · Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Japan. · Department of Medical Oncology, St. Marianna University School of Medicine Hospital, Japan. ·Intern Med · Pubmed #31243233.

ABSTRACT: Gemcitabine plus nab-paclitaxel is the current standard chemotherapy for patients with metastatic pancreatic cancer. We conducted a phase I/II study in Japan, in which high response rates and manageable toxicity were observed. In this study, two patients were reported as experiencing pancreatitis due to chemotherapy. In general, pancreatitis is sometimes observed when the tumor involves the pancreatic duct, and the onset is observed before the diagnosis or at the initial stage. The onset of pancreatitis in these cases was unique and observed after the start of chemotherapy. Pancreatitis may be induced by the alleviation of stenosis of the pancreatic duct associated with tumor shrinkage.

5 Clinical Trial A phase II study of modified FOLFIRINOX for chemotherapy-naïve patients with metastatic pancreatic cancer. 2018

Ozaka, Masato / Ishii, Hiroshi / Sato, Tosiya / Ueno, Makoto / Ikeda, Masafumi / Uesugi, Kazuhiro / Sata, Naohiro / Miyashita, Kouichirou / Mizuno, Nobumasa / Tsuji, Kunihiro / Okusaka, Takuji / Furuse, Junji. ·Department of Gastroenterology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. masato.ozaka@jfcr.or.jp. · National Hospital Organization Shikoku Cancer Center, 160 Kou, Minami Umemoto, Matsuyama, 791-0280, Japan. · Department of Biostatistics, Kyoto University School of Public Health, Yoshida-honmachi, Sakyo-ku, Kyoto, 606-8501, Japan. · Division of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa, 241-8515, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. · Department of Surgery, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan. · Internal Medicine of Gastroenterology, Showa University Northern Yokohama Hospital, Tsudukiku, Chigasakityuo 35-1, Yokohama, Kanagawa, 224-8503, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. · Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Kuratsukihigashi 2-1, Kanazawa, Ishikawa, 920-8530, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. · Department of Medical Oncology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo, 181-8611, Japan. ·Cancer Chemother Pharmacol · Pubmed #29633005.

ABSTRACT: BACKGROUND: We evaluated the efficacy and safety of a modified FOLFIRINOX regimen for chemotherapy-naïve patients with metastatic pancreatic cancer. METHODS: Patients with untreated metastatic pancreatic cancer (MPC) received modified FOLFIRINOX (intravenous oxaliplatin 85 mg/m RESULTS: Sixty-nine pts. were enrolled from 39 institutions in Japan. The median overall survival was 11.2 months [95% confidence interval (CI) 9.0-]. The median progression-free survival was 5.5 months (95% CI 4.1-6.7). The response rate was 37.7% (95% CI 26.3-50.2), and the disease control rate was 78.3% (95% CI 66.7-87.3). The incidence of grade 3 or higher neutropenia was 47.8%. Serious adverse events occurred in six patients (8.7%). All AE proportions were less than those in the previous Japanese full-dose phase II study. One patient died due to interstitial pneumonia related to treatment. CONCLUSION: This is the first prospective study of modified FOLFIRINOX in Asia. Modified FOLFIRINOX in this study has an improved safety profile with maintained efficacy in MPC without prophylactic pegfilgrastim.

6 Clinical Trial A randomized phase II study of gemcitabine plus Z-360, a CCK2 receptor-selective antagonist, in patients with metastatic pancreatic cancer as compared with gemcitabine plus placebo. 2017

Ueno, Makoto / Li, Chung Pin / Ikeda, Masafumi / Ishii, Hiroshi / Mizuno, Nobumasa / Yamaguchi, Taketo / Ioka, Tatsuya / Oh, Do Youn / Ichikawa, Wataru / Okusaka, Takuji / Matsuyama, Yutaka / Arai, Daichi / Chen, Li Tzong / Park, Young Suk / Furuse, Junji. ·Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, 2-3-2, Nakao, Asahi-ku, Yokohama-shi, Kanagawa, 241-8515, Japan. uenom@kcch.jp. · Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, 201, Section 2, Shin-Pai Road, Taipei, 11217, Taiwan. · School of Medicine, National Yang-Ming University, 155, Section 2, Linong Street, Taipei, 112, Taiwan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan. · Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan. · Department of Gastroenterology, Clinical Research Center, National Hospital Organization Shikoku Cancer Center, 160, Kou, Minamiumemoto-machi, Matsuyama-shi, Ehime, 791-0280, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan. · Department of Gastroenterology, Chiba Cancer Center, 666-2 Nitona-cho, Chuo-ku, Chiba-shi, Chiba, 260-8717, Japan. · Department of Gastrointestinal Cancer Screening and Surveillance, Osaka Medical Center for Cancer and Cardiovascular Disease, 3-3 Nakamichi 1-Chome, Higashinari-ku, Osaka, 537-8511, Japan. · Department of Gastrointestinal Cancer Screening and Surveillance, Osaka International Cancer Institute, 3-1-69, Otemae, Chuo-ku, Osaka, 541-8567, Japan. · Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea. · Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, 1-30 Fujigaoka, Aoba-ku, Yokohama, Kanagawa, 227-8501, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. · Department of Biostatistics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan. · Division of Clinical Research 3, ZERIA Pharmaceutical Co., Ltd., 10-11, Nihonbashi Kobuna-cho, Chuo-ku, Tokyo, 103-8351, Japan. · National Institute of Cancer Research, National Health Research Institutes, 367, Sheng-Li Rd., North District, 70456, Tainan, Taiwan. · Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Irwon-Dong, Gangnam-Gu, Seoul, 06351, South Korea. · Department of Internal Medicine, Medical Oncology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan. ·Cancer Chemother Pharmacol · Pubmed #28634650.

ABSTRACT: BACKGROUND: We investigated the efficacy and safety of 60, 120, or 240 mg of Z-360, which is a highly potent cholecystokinin2-receptor-selective antagonist, combined with gemcitabine in patients with metastatic pancreatic cancer. METHODS: Patients were randomly assigned in a 1:1:1:1 ratio to one of four treatment groups. Patients received 1000 mg/m RESULTS: The median OS was 1.3 months longer in the GZ 60 mg group compared with the Gem group (8.5 vs. 7.2 months) and the risk of death was reduced by 19% compared with the Gem group, although there were no statistically significant differences. The study treatments were well tolerated. CONCLUSIONS: In this Phase II study, no statistically significant differences between the GZ groups and Gem group were detected in any analysis. However, Z-360 in dose of 60 mg tends to improve OS in patients with metastatic pancreatic cancer with low toxic effect. Further exploratory trials with other agents such as gemcitabine plus nab-paclitaxel might be beneficial.

7 Clinical Trial Unexpected Side Effects of a High S-1 Dose: Subanalysis of a Phase III Trial Comparing Gemcitabine, S-1 and Combinatorial Treatments for Advanced Pancreatic Cancer. 2016

Kobayashi, Satoshi / Ueno, Makoto / Hara, Hiroki / Irie, Kuniyasu / Goda, Yoshihiro / Moriya, Satoshi / Tezuka, Shun / Tanaka, Masao / Okusaka, Takuji / Ohkawa, Shinichi / Morimoto, Manabu. ·Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama City, Japan. ·Oncology · Pubmed #27303788.

ABSTRACT: OBJECTIVE: In this subanalysis of a phase III trial using three categorized doses of S-1, the influence of the actual doses on safety and efficacy was evaluated. METHODS: We compared the efficacy and safety of the S-1 or gemcitabine plus S-1 combination (GS) arm between the top 10% group and the bottom 10% group according to the initial doses of S-1: ≥77.6 versus ≤65.9 mg/m2/day (n = 28 vs. 28) in the S-1 arm, and ≥65.1 versus ≤53.8 mg/m2/day (n = 27 vs. 28) in the GS arm. RESULTS: Overall and progression-free survival were not significantly different between these two groups: hazard ratios of 0.818 and 0.761 with p values of 0.498 and 0.330 in the S-1 arm, and hazard ratios of 0.836 and 0.759 with p values of 0.557 and 0.323 in the GS arm, respectively. Incidences of grade 3-4 hematological toxicities were significantly higher in the top 10% group than in the bottom 10% group: 42.9 versus 14.3 and 85.2 versus 57.1%, with p values of 0.037 and 0.037 in the S-1 and the GS combination arm, respectively. CONCLUSIONS: Higher actual doses of S-1 were associated with a higher incidence of hematological toxicity even in the same dose setting.

8 Clinical Trial Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. 2016

Ueno, Hideki / Ikeda, Masafumi / Ueno, Makoto / Mizuno, Nobumasa / Ioka, Tatsuya / Omuro, Yasushi / Nakajima, Takako Eguchi / Furuse, Junji. ·Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. hiueno@ncc.go.jp. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. · Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. · Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. · Department of Medical Oncology, St.Marianna University School of Medicine Hospital, Kawasaki, Japan. · Department of Medical Oncology, Kyorin University School of Medicine, Tokyo, Japan. ·Cancer Chemother Pharmacol · Pubmed #26842789.

ABSTRACT: PURPOSE: Efficacy and safety of nab-paclitaxel plus gemcitabine have not been clarified in Japanese patients with metastatic pancreatic cancer. No pharmacokinetic profile of co-administration of nab-paclitaxel and gemcitabine has been reported. We conducted a phase I/II study of the efficacy, safety, and pharmacokinetics in Japanese patients with metastatic pancreatic cancer. METHODS: The patients were administered 125 mg/m(2) nab-paclitaxel followed by 1000 mg/m(2) gemcitabine on day 1, 8, and 15 every 4 weeks. Treatment was continued until disease progression, unacceptable adverse events, or withdrawal of consent, whichever occurred first. The primary endpoints were tolerability in phase I and overall response rate according to RECIST in phase II. RESULTS: A total of 34 patients were enrolled. At the time of 1-year follow-up analysis since the last patient enrollment, the objective response rate by independent review committee was 58.8% (20 of 34 patients; 95% confidence interval [CI], 40.7-75.4%). The median progression-free survival and median overall survival were 6.5 months (95% CI, 5.1-8.3) and 13.5 months (95% CI, 10.6--not reached), respectively. Main adverse drug reactions of grade 3 or higher were neutropenia (70.6%), leukopenia (55.9%), anemia (14.7%), lymphocytopenia (14.7%), thrombocytopenia (14.7%), and peripheral sensory neuropathy (11.8%). There were no treatment-related deaths and no marked differences in pharmacokinetics of combined paclitaxel and gemcitabine in historical comparison between co-administration and monotherapies. CONCLUSIONS: Nab-paclitaxel plus gemcitabine regimen showed highly promising efficacy with manageable safety profile under careful observation and with appropriate supportive care in Japanese patients with metastatic pancreatic cancer. CLINICAL TRIAL NUMBER: JapicCTI-121987.

9 Clinical Trial Potential prognostic significance of a new proteomic profile in patients with advanced pancreatic adenocarcinoma. 2015

Kobayashi, Satoshi / Ueno, Makoto / Irie, Kuniyasu / Goda, Yoshihiro / Aoyama, Toru / Morinaga, Soichiro / Ohkawa, Shinichi / Morimoto, Manabu. ·Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Japan. Electronic address: kobayashis@kcch.jp. · Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Japan. · Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Japan. ·Pancreatology · Pubmed #26255025.

ABSTRACT: OBJECTIVES: Seven-signal proteomic approach has recently been developed as a new proteomic profile measured by matrix-assisted laser desorption/ionization mass spectrometry. The aim of this study was to evaluate prognostic significance of this proteomic value in patients with pancreatic adenocarcinoma. METHODS: Blood samples from the patients with pancreatic adenocarcinoma were prospectively collected before treatments including surgical resection and systemic chemotherapies. The seven-signal proteomic profiles of the samples were measured, and the prognostic significance of the proteomic value was evaluated through comparison with other existing prognostic markers. RESULTS: Cut-off value of the proteomic profiles at 52 stratified overall prognosis of the patients (6.5 months vs. 10.9 months with the values ≥52 vs. <52, p = 0.020). In subgroup analyses of inoperable cases with carcinoembryonic antigen level of <5 ng/ml or performance status of 0-1, the proteomic value at 52 stratified their prognosis (p = 0.002 and p = 0.006, respectively). CONCLUSIONS: The new seven-signal proteomics showed useful prognostic significance for patients with pancreatic adenocarcinoma. Further studies with a large sample size would be required to evaluate whether this proteomic approach possibly complements the existing parameters, such as carcinoembryonic antigen and performance status.

10 Clinical Trial Glasgow Prognostic Score Predicts Clinical Outcomes in Patients with Pancreatic Cancer Undergoing Adjuvant Gemcitabine Monotherapy After Curative Surgery. 2015

Morinaga, Soichiro / Murakawa, Masaaki / Katayama, Yusuke / Yamaoku, Koichiro / Aoyama, Toru / Kanazawa, Amane / Higuchi, Akio / Shiozawa, Manabu / Kobayashi, Satoshi / Ueno, Makoto / Morimoto, Manabu. ·Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Asahiku, Yokohama, Japan morinagas@kcch.jp. · Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Asahiku, Yokohama, Japan. · Department of Gastrointestinal Medicine, Kanagawa Cancer Center, Asahiku, Yokohama, Japan. ·Anticancer Res · Pubmed #26254380.

ABSTRACT: BACKGROUND/AIM: The Glasgow Prognostic Score (GPS), an inflammation-based prognostic score, has been shown to predict the clinical outcomes of a variety of cancer types. The aim of this study was to determine whether the GPS predicts clinical outcomes of patients with pancreatic cancer treated with adjuvant chemotherapy after surgery. PATIENTS AND METHODS: Forty patients resected for pancreatic cancer who underwent adjuvant gemcitabine monotherapy after curative surgery were included. The GPS was measured prior to adjuvant therapy and correlated with clinical outcomes. RESULTS: The disease-free survival (DFS) and overall survival (OS) in patients with an elevated GPS (GPS1 or GPS2) were significantly poorer (p=0.001 and p=0.035, respectively, by log-rank test) than patients with a GPS of 0. An elevated GPS was found to be independently associated with poor DFS (p=0.002, by Cox regression model). CONCLUSION: The pre-adjuvant GPS may predict clinical outcome in patients with pancreatic cancer undergoing adjuvant chemotherapy after surgery.

11 Clinical Trial Possibility of immunotherapy for biliary tract cancer: how do we prove efficacy? Introduction to a current ongoing phase I and randomized phase II study to evaluate the efficacy and safety of adding Wilms tumor 1 peptide vaccine to gemcitabine and cisplatin for the treatment of advanced biliary tract cancer (WT-BT trial). 2012

Okusaka, Takuji / Ueno, Makoto / Sato, Tosiya / Heike, Yuji. ·Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. tokusaka@ncc.go.jp ·J Hepatobiliary Pancreat Sci · Pubmed #22273718.

ABSTRACT: BACKGROUND/PURPOSE: In biliary tract cancer, few clinical studies evaluating immunotherapy have been reported. A phase I and randomized phase II study with Wilms tumor 1 (WT1) peptide vaccine plus gemcitabine and cisplatin (GC) for chemo-naïve patients with unresectable or recurrent biliary tract cancer was started, because the overexpression of WT1 is seen in the majority of patients with this disease, encouraging the potential of WT1-based immunotherapy. This trial was registered at the UMIN Clinical Trials Registry as UMIN 000004886. METHODS AND RESULTS: The aim of this trial is to evaluate the efficacy and safety of the regimen and to determine whether the regimen should be compared with the current standard regimen, GC, in a subsequent phase III trial for patients with unresectable or recurrent biliary tract cancer. Six patients in the phase I study and a total of 100 patients in the phase II study will be accrued over a 2-year period. The patients in the phase II study will be randomized at a 2:1 ratio to receive GC either with or without WT1 peptide vaccine. The primary endpoint of the phase II study is the 1-year overall survival rate. CONCLUSIONS: This is the first randomized trial to evaluate the use of immunotherapy in patients with advanced biliary tract cancer.

12 Clinical Trial Phase I/II study of gemcitabine as a fixed dose rate infusion and S-1 combination therapy (FGS) in gemcitabine-refractory pancreatic cancer patients. 2012

Morizane, Chigusa / Okusaka, Takuji / Ueno, Hideki / Kondo, Shunsuke / Ikeda, Masafumi / Furuse, Junji / Shinichi, Ohkawa / Nakachi, Kohei / Mitsunaga, Shuichi / Kojima, Yasushi / Suzuki, Eiichiro / Ueno, Makoto / Yamaguchi, Tomohiro. ·Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. cmorizan@ncc.go.jp ·Cancer Chemother Pharmacol · Pubmed #22120961.

ABSTRACT: PURPOSE: There is no standard regimen for gemcitabine (Gem)-refractory pancreatic cancer (PC) patients. In a previous phase II trial, S-1 was found to exhibit marginal efficacy. Gem administration by fixed dose rate infusion of 10 mg/m(2)/min (FDR-Gem) should maximize the rate of intracellular accumulation of gemcitabine triphosphate and might improve clinical efficacy. We conducted the phase I/II of FDR-Gem and S-1 (FGS) in patients with Gem-refractory PC. METHODS: The patients received FDR-Gem on day 1 and S-1 orally twice daily on days 1-7. Cycles were repeated every 14 days. Patients were scheduled to receive Gem (mg/m(2)/week) and S-1 (mg/m(2)/day) at four dose levels in the phase I: 800/80 (level 1), 1,000/80 (level 2), 1,200/80 (level 3) and 1,200/100 (level 4). Forty patients were enrolled in the phase II study at recommended dose. RESULTS: The recommended dose was the level 3. In the phase II, a partial response has been confirmed in seven patients (18%). The median overall survival time and median progression-free survival time are 7.0 and 2.8 months, respectively. The common adverse reactions were anorexia, leukocytopenia and neutropenia. CONCLUSION: This combination regimen of FGS is active and well tolerated in patients with Gem-refractory PC.

13 Article A randomized phase II study of nutritional and exercise treatment for elderly patients with advanced non-small cell lung or pancreatic cancer: the NEXTAC-TWO study protocol. 2019

Miura, Satoru / Naito, Tateaki / Mitsunaga, Shuichi / Omae, Katsuhiro / Mori, Keita / Inano, Toshimi / Yamaguchi, Teiko / Tatematsu, Noriatsu / Okayama, Taro / Morikawa, Ayumu / Mouri, Takako / Tanaka, Hisashi / Kimura, Madoka / Imai, Hisao / Mizukami, Takuro / Imoto, Akira / Kondoh, Chihiro / Shiotsu, Shinsuke / Okuyama, Hiroyuki / Ueno, Makoto / Takahashi, Toshiaki / Tsuji, Tetsuya / Aragane, Hideki / Inui, Akio / Higashiguchi, Takashi / Takayama, Koichi. ·Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan. · Department of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. t.naito@scchr.jp. · Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. · Department of Clinical Biostatistics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Clinical Research Center, Shizuoka Cancer Center, Nagaizumi, Japan. · Division of Nutrition, Shizuoka Cancer Center, Nagaizumi, Japan. · Department of Health Sciences, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. · Department of Rehabilitation Medicine, National Cancer Center Hospital East, Kashiwa, Japan. · Division of Rehabilitation Medicine, Shizuoka Cancer Center, Shizuoka, Japan. · Division of Nursing, Shizuoka Cancer Center, Shizuoka, Japan. · Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. · Department of Respiratory Medicine, Hirosaki University, Hirosaki, Japan. · Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan. · Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Gunma, Japan. · Department of Clinical Oncology, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, Japan. · Second Department of Internal Medicine, Osaka Medical College, Osaka, Japan. · Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan. · Department of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan. · Department of Clinical Oncology, Kagawa University Hospital, Kagawa, Japan. · Department of Gastroenterology, Kanagawa Cancer Center, Kanagawa, Japan. · Department of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. · Department of Rehabilitation Medicine, Keio University School of Medicine, Tokyo, Japan. · Department of Surgery, Aiseikai Yamashina Hospital, Kyoto, Japan. · Pharmacological Department of Herbal Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan. · Department of Surgery and Palliative Medicine, Fujita Health University School of Medicine, Aichi, Japan. ·BMC Cancer · Pubmed #31151425.

ABSTRACT: BACKGROUND: Most advanced elderly cancer patients experience fatigue, anorexia, and declining physical function due to cancer cachexia, for which effective interventions have not been established. We performed a phase I study of a new nonpharmacological multimodal intervention called the nutritional and exercise treatment for advanced cancer (NEXTAC) program and reported the excellent feasibility of and compliance with this program in elderly patients with advanced cancer who were at risk for cancer cachexia. We report here the background, hypothesis, and design of the next-step multicenter, randomized phase II study to evaluate the efficacy of the program, the NEXTAC-TWO study. METHODS: Patients with chemo-naïve advanced non-small cell lung cancer or pancreatic cancer, age ≥ 70 years, performance status ≤2, with adequate organ function and without disability according to the modified Katz index will be eligible. In total, 130 participants will be recruited from 15 Japanese institutions and will be randomized into either the intervention group or a control group. Computer-generated random numbers are allocated to each participant. Stratification factors include performance status (0 to 1 vs. 2), site of primary cancer (lung vs. pancreas), stage (III vs. IV), and type of chemotherapy (cytotoxic vs. others). Interventions and assessment will be performed 4 times every 4 ± 2 weeks from the date of randomization. Interventions will consist of nutritional counseling, nutritional supplements (rich in branched-chain amino acids), and a home-based exercise program. The exercise program will include low-intensity daily muscle training and lifestyle education to promote physical activity. The primary endpoint is disability-free survival. It is defined as the period from the date of randomization to the date of developing disability or death due to any cause. This trial also plans to evaluate the improvements in nutritional status, physical condition, quality of life, activities of daily living, overall survival, and safety as secondary endpoints. Enrollment began in August 2017. The study results will demonstrate the efficacy of multimodal interventions for elderly cancer patients and their application for the maintenance of physical and nutritional conditions in patients with cancer cachexia. This work is supported by a grant-in-aid from the Japan Agency for Medical Research and Development. DISCUSSION: This is the first randomized trial to evaluate the efficacy and safety of a multimodal intervention specific for elderly patients with advanced cancer. TRIAL REGISTRATION: Registered at August 23, 2017. Registry number: UMIN000028801 .

14 Article A double-blind randomized comparative clinical trial to evaluate the safety and efficacy of dendritic cell vaccine loaded with WT1 peptides (TLP0-001) in combination with S-1 in patients with advanced pancreatic cancer refractory to standard chemotherapy. 2019

Katsuda, Masahiro / Miyazawa, Motoki / Ojima, Toshiyasu / Katanuma, Akio / Hakamada, Kenichi / Sudo, Kentaro / Asahara, Shingo / Endo, Itaru / Ueno, Makoto / Hara, Kazuo / Yamada, Suguru / Fujii, Tsutomu / Satoi, Sohei / Ioka, Tatsuya / Ohira, Masaichi / Akahori, Takahiro / Kitano, Masayuki / Nagano, Hiroaki / Furukawa, Masayuki / Adachi, Tomohiko / Yamaue, Hiroki. ·Second Department of Surgery, Wakayama Medical University, School of Medicine, 811-1, Kimiidera, Wakayama, 641-8510, Japan. · Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan. · Department of Gastroenterological Surgery, Hirosaki University, Graduate School of Medicine, Aomori, Japan. · Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan. · Department of Gastroenterology, Chiba Tokushukai Hospital, Chiba, Japan. · Department of Gastroenterological Surgery, Yokohama City University, Graduate School of Medicine, Yokohama, Japan. · Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Department of Gastroenterological Surgery (Surgery II), Nagoya University, Graduate School of Medicine, Nagoya, Japan. · Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. · Department of Surgery, Kansai Medical University, Hirakata, Japan. · Department of Cancer Survey and Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan. · Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Osaka, Japan. · Department of Surgery, Nara Medical University, Nara, Japan. · Second Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama, Japan. · Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University, Graduate School of Medicine, Ube, Japan. · Department of Hepato-Biliary-Pancreatology, Kyushu Cancer Center, Fukuoka, Japan. · Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. · Second Department of Surgery, Wakayama Medical University, School of Medicine, 811-1, Kimiidera, Wakayama, 641-8510, Japan. yamaue-h@wakayama-med.ac.jp. ·Trials · Pubmed #31029154.

ABSTRACT: BACKGROUND: Pancreatic cancer is a refractory malignancy, and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms' tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy. METHODS: This is an investigator-initiated, double-blind, comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines. DISCUSSION: Clinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety, as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000027179 . Registered on 9 April 2017.

15 Article Surgery for Pancreatic Neuroendocrine Tumor G3 and Carcinoma G3 Should be Considered Separately. 2019

Yoshida, Tsukasa / Hijioka, Susumu / Hosoda, Waki / Ueno, Makoto / Furukawa, Masayuki / Kobayashi, Noritoshi / Ikeda, Masafumi / Ito, Tetsuhide / Kodama, Yuzo / Morizane, Chigusa / Notohara, Kenji / Taguchi, Hiroki / Kitano, Masayuki / Yane, Kei / Tsuchiya, Yoshiaki / Komoto, Izumi / Tanaka, Hiroki / Tsuji, Akihito / Hashigo, Syunpei / Mine, Tetsuya / Kanno, Atsushi / Murohisa, Go / Miyabe, Katsuyuki / Takagi, Tadayuki / Matayoshi, Nobutaka / Sakaguchi, Masafumi / Ishii, Hiroshi / Kojima, Yasushi / Matsuo, Keitaro / Yoshitomi, Hideyuki / Nakamori, Shoji / Yanagimoto, Hiroaki / Yatabe, Yasushi / Furuse, Junji / Mizuno, Nobumasa. ·Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Department of Gastroenterology, Kizawa Memorial Hospital, Minokamo, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. shijioka@ncc.go.jp. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. shijioka@ncc.go.jp. · Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan. · Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Yokohama, Japan. · Department of Hepato-Biliary-Pancreatology, National Kyushu Cancer Center, Fukuoka, Japan. · Department of Oncology, Yokohama City University Hospital, Yokohama, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. · Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan. · Department of Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. · Department of Gastroenterology and Hepatology, Kinki University, Faculty of Medicine, Sayama, Japan. · Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan. · Department of Digestive Surgery, Niigata Cancer Center Hospital, Niigata, Japan. · Department of Surgery, Kansai Electric Power Hospital, Osaka, Japan. · Department of Gastroenterology, Suzuka General Hospital, Suzuka, Japan. · Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, Japan. · Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. · Department of Gastroenterology, Tokai University School of Medicine, Isehara, Japan. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. · Department of Gastroenterology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan. · Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. · Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan. · Department of Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. · Department of Gastroenterology, Saiseikai Kumamoto Hospital, Kumamoto, Japan. · Department of Gastroenterology, Shikoku Cancer Center, Matsuyama, Japan. · Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. · Department of Gastroenterology, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan. · Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan. · Department of General Surgery, Chiba University, Graduate School of Medicine, Chiba, Japan. · Department of Hepato-biliary-Pancreatic Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan. · Department of Surgery, Kansai Medical University Hospital, Maikata, Japan. · Department of Medical Oncology, Kyorin University Faculty of Medicine, Mitaka, Japan. ·Ann Surg Oncol · Pubmed #30863939.

ABSTRACT: BACKGROUND: The role of surgery in pancreatic neuroendocrine neoplasm grade 3 (pNEN-G3) treatment remains unclear. We aimed to clarify the role of surgery for pNEN-G3, which has recently been reclassified as pancreatic neuroendocrine tumor-G3 (pNET-G3) and pancreatic neuroendocrine carcinoma-G3 (pNEC-G3), with and without metastases, respectively. METHODS: We analyzed a subgroup of patients from the Japanese pancreatic NEC study, a Japanese multicenter case-series study of pNEN-G3. Pathologists subclassified 67 patients as having pNET-G3 or pNEC-G3 based on morphological features. We compared the overall survival (OS) rates among patients who were grouped according to whether they had undergone tumor-targeted surgery for tumors without (SwoM) or with (SwM) metastases, or non-surgical procedures (NS). RESULTS: Data from 21 patients with pNET-G3 (SwoM, n = 6; SwM, n = 5; NS, n = 10) and 46 patients with pNEC-G3 (SwoM, n = 8; SwM, n = 5; NS, n = 33) were analyzed. OS of patients with pNET-G3 was significantly longer after SwoM and SwM than with NS (p = 0.018 and p = 0.022). In contrast, OS did not significantly differ between either SwoM or SwM and NS (p = 0.093 and p = 0.489) among patients with pNEC-G3. CONCLUSION: The role of surgery should be considered separately for pNET-G3 and pNEC-G3. Although SwoM and SwM can be considered for pNET-G3, caution is advised before considering SwM and SwoM for pNEC-G3.

16 Article The impact of SPARC expression on the survival of pancreatic ductal adenocarcinoma patients after curative resection. 2019

Murakawa, Masaaki / Aoyama, Toru / Miyagi, Yohei / Kobayashi, Satoshi / Ueno, Makoto / Morimoto, Manabu / Numata, Masakatsu / Yamamoto, Naoto / Tamagawa, Hiroshi / Yukawa, Norio / Rino, Yasushi / Masuda, Munetaka / Morinaga, Soichiro. ·Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan. · Department of Surgery, Yokohama City University. · Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute. · Department of Hepatobiliary Pancreatic Oncology, Kanagawa Cancer Center. ·J Cancer · Pubmed #30719160.

ABSTRACT:

17 Article TAS-118 (S-1 plus leucovorin) versus S-1 in patients with gemcitabine-refractory advanced pancreatic cancer: a randomised, open-label, phase 3 study (GRAPE trial). 2019

Ioka, Tatsuya / Ueno, Makoto / Ueno, Hideki / Park, Joon Oh / Chang, Heung-Moon / Sasahira, Naoki / Kanai, Masashi / Chung, Ik Joo / Ikeda, Masafumi / Nakamori, Shoji / Mizuno, Nobumasa / Omuro, Yasushi / Yamaguchi, Taketo / Hara, Hiroki / Sugimori, Kazuya / Furuse, Junji / Maguchi, Hiroyuki / Furukawa, Masayuki / Fukuzawa, Kengo / Kim, Jun-Suk / Yukisawa, Seigo / Takeuchi, Masahiro / Okusaka, Takuji / Boku, Narikazu / Hyodo, Ichinosuke. ·Department of Cancer Survey and Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan. · Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. · Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. · Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. · Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan. · Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, South Korea. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. · Department of Hepatobiliary and Pancreatic Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. · Department of Gastroenterology, Chiba Cancer Center, Chiba, Japan. · Department of Gastroenterology, Saitama Cancer Center Hospital, Saitama, Japan. · Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan. · Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan. · Center of Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan. · Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. · Department of Surgery, Oita Red Cross Hospital, Oita, Japan. · Department of Oncology and Hematology, Korea University Guro Hospital, Seoul, South Korea. · Department of Medical Oncology, Tochigi Cancer Center, Utsunomiya, Japan. · Department of Clinical Medicine, School of Pharmacy (Biostatistics), Kitasato University, Tokyo, Japan. · Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. · Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. Electronic address: ihyodo@md.tsukuba.ac.jp. ·Eur J Cancer · Pubmed #30471651.

ABSTRACT: BACKGROUND: In our previous randomised phase 2 study for patients with gemcitabine-refractory advanced pancreatic cancer, S-1 plus leucovorin improved progression-free survival compared with S-1 alone. Here, we evaluated the efficacy of TAS-118 (S-1 plus leucovorin) versus S-1 in overall survival (OS). PATIENTS AND METHODS: This randomised, open-label, phase 3 study was conducted at 58 centres in Japan and Korea. Patients with metastatic pancreatic cancer that progressed during first-line gemcitabine-based chemotherapy or recurred during or after post-operative gemcitabine-based adjuvant treatment were randomly assigned (1:1) to receive either S-1 (40-60 mg, twice daily for 4 weeks in a 6-week cycle) or TAS-118 (S-1 40-60 mg plus leucovorin 25 mg, twice daily for 1 week in a 2-week cycle). The primary end-point was OS. RESULTS: A total of 603 patients were randomised, and 300 and 301 patients received TAS-118 and S-1, respectively. There was no difference in OS between groups (median OS for TAS-118 versus S-1, 7.6 months versus 7.9 months; hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.82-1.16]; P = 0.756). Progression-free survival was significantly longer with TAS-118 than S-1 (median, 3.9 months versus 2.8 months; HR, 0.80 [95% CI, 0.67-0.95]; P = 0.009). There were interactions between Japan and Korea (P = 0.004) and between unresectable and recurrent disease (P = 0.025) in OS. Incidence, profile and severity of adverse events were similar between groups. CONCLUSION: TAS-118 did not improve OS in patients with gemcitabine-refractory advanced pancreatic cancer compared to S-1. Further studies are needed to find patients who have benefit from adding leucovorin to S-1.

18 Article Survival and the prognosticators of peritoneal cytology-positive pancreatic cancer patients undergoing curative resection followed by adjuvant chemotherapy. 2018

Aoyama, Toru / Atsumi, Yosuke / Kazama, Keisuke / Murakawa, Masaaki / Shiozawa, Manabu / Kobayashi, Satoshi / Ueno, Makoto / Morimoto, Manabu / Yukawa, Norio / Oshima, Takashi / Yoshikawa, Takaki / Rino, Yasushi / Masuda, Munetaka / Morinaga, Soichiro. ·Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan. · Department of Hepatobiliary Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Japan. · Department of Surgery, Yokohama City University, Yokohama, Japan. ·J Cancer Res Ther · Pubmed #30539858.

ABSTRACT: Background: The factors associated with the survival and prognosis of peritoneal cytology (CY)-positive pancreatic cancer patients who undergo curative resection followed by adjuvant chemotherapy have not been established. Patients and Methods: Both overall survival (OS) and recurrence-free survival (RFS) were examined in 23 peritoneal CY-positive pancreatic cancer patients who underwent curative resection followed by adjuvant chemotherapy between 2005 and 2015. Results: When the length of OS was evaluated using a log-rank test, significant differences were observed in the number of metastatic lymph nodes. In addition, univariate and multivariate analyses demonstrated that the number of metastatic lymph nodes was a significant independent risk factor for OS and a marginally significant risk factor for RFS. The 3-year OS rate was 20.2% in patients with ≤8 metastatic lymph nodes, and it was 0% in those with the ≥9 metastatic lymph nodes (P = 0.017). The 3-year RFS rate was 6.3% in patients with ≤8 metastatic lymph nodes, whereas it was 0% in those with ≥9 metastatic lymph nodes (P = 0.062). Conclusions: The number of metastatic lymph nodes is the most important prognostic factor for OS and RFS in peritoneal CY-positive pancreatic cancer patients who underwent curative resection followed by adjuvant chemotherapy. To improve the survival of these patients, it is necessary to establish optimal treatments.

19 Article Predictive value of ERCC1, ERCC2, ERCC4, and glutathione S-Transferase Pi expression for the efficacy and safety of FOLFIRINOX in patients with unresectable pancreatic cancer. 2018

Tezuka, Shun / Ueno, Makoto / Kobayashi, Satoshi / Morimoto, Manabu / Ohkawa, Shinichi / Hirotani, Akane / Tozuka, Yuichiro / Moriya, Satoshi / Nakamura, Yoshiyasu / Miyagi, Yohei / Sugimori, Makoto / Maeda, Shin. ·Department of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Yokohama, Japan. · Department of Molecular Pathology and Genetics, Kanagawa Cancer Center Research Institute Yokohama, Japan. · Department of Gastroenterology, Yokohama City University Graduate School of Medicine Yokohama, Japan. ·Am J Cancer Res · Pubmed #30416859.

ABSTRACT: The platinum-based chemotherapy regimen FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) is currently used as a standard treatment for patients with unresectable pancreatic cancer. FOLFIRINOX is associated with severe toxicities, including neutropenia, febrile neutropenia, and anorexia; however, there are currently no reliable biomarkers to predict its efficacy and safety. Several studies of patients with various cancers have shown that tumor expression of excision repair cross-complementing (ERCC) proteins and glutathione S-transferase Pi (GSTPi) correlates with the response to platinum-based chemotherapies. Therefore, in this study, we examined the associations between expression of ERCC proteins and GSTPi and the safety and efficacy of FOLFIRINOX in 34 patients with unresectable pancreatic cancer. ERCC1, ERCC2, ERCC4, and GSTPi expression were examined by immunohistochemical staining of tumor specimens and the results were correlated with overall survival, progression-free survival, response rate, disease control rate, and the frequency of grade 3-4 neutropenia and non-hematologic toxicities. We found that ERCC1, ERCC2, ERCC4, and GSTPi were expressed in tumor samples from 64%, 24%, 18%, and 64% of patients, respectively. Notably, there were no statistically significant associations between the expression pattern of any of the proteins and either the clinical outcomes or the frequency of grade 3-4 neutropenia or grade 3-4 anorexia. Collectively, these data indicate that tumor expression of ERCC1, ERCC2, ERCC4, and GSTPi does not predict the safety or efficacy of FOLFIRINOX in patients with pancreatic cancer.

20 Article Safety and feasibility of enhanced recovery after surgery in the patients underwent distal pancreatectomy for pancreatic cancer. 2018

Aoyama, Toru / Kazama, Keisuke / Murakawa, Masaaki / Atsumi, Yosuke / Shiozawa, Manabu / Ueno, Makoto / Morimoto, Manabu / Taniguchi, Hideki / Masuda, Munetaka / Morinaga, Soichiro. ·Department of Gastrointestinal Surgery, Kanagawa Cancer Center; Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan. · Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan. · Department of Hepatobiliary Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan. · Department of Anesthesiology, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan. · Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan. ·J Cancer Res Ther · Pubmed #30249894.

ABSTRACT: Purpose: This study assessed whether our enhanced recovery after surgery (ERAS) program for distal pancreatectomy (DP) is safe and feasible. Patients and Methods: The subjects were patients who underwent consecutive DP between 2012 and 2014 at the Department of Gastrointestinal Surgery, Kanagawa Cancer Center. They received perioperative care according to ERAS program. All data were retrieved retrospectively. Outcome measures included postoperative mortality, morbidity, hospitalization, and 30-day readmission rate. Our ERAS program included 12 elements (4 preoperative elements, 3 intraoperative elements, and 5 postoperative elements). Results: A total of 44 patients were studied. The overall incidence of morbidity was 29.5%, the incidence of mortality was 0%, and the incidence of readmission was 0%. Four preoperative elements and 3 intraoperative elements seemed feasible. Among the 5 postoperative elements, 4 elements seemed feasible, accounting 90%< performance rate however the early removal of catheters and drain seemed not feasible. The median postoperative hospital stay was 14 days (range: 8-39 days). The median postoperative hospital stay was 13 days (range: 8-27 days) in patients without postoperative complications while the median postoperative hospital stay was 26 days (range: 14-39 days) in patients with postoperative complications. Conclusion: This study results suggested that our ERAS program is safe and feasible in patients who undergo DP. However, achieving compliance on the postoperative element, especially the removal of catcher and drain, was more challenging.

21 Article Prediction model for pancreatic cancer risk in the general Japanese population. 2018

Nakatochi, Masahiro / Lin, Yingsong / Ito, Hidemi / Hara, Kazuo / Kinoshita, Fumie / Kobayashi, Yumiko / Ishii, Hiroshi / Ozaka, Masato / Sasaki, Takashi / Sasahira, Naoki / Morimoto, Manabu / Kobayashi, Satoshi / Ueno, Makoto / Ohkawa, Shinichi / Egawa, Naoto / Kuruma, Sawako / Mori, Mitsuru / Nakao, Haruhisa / Wang, Chaochen / Nishiyama, Takeshi / Kawaguchi, Takahisa / Takahashi, Meiko / Matsuda, Fumihiko / Kikuchi, Shogo / Matsuo, Keitaro. ·Division of Data Science, Data Coordinating Center, Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan. · Department of Public Health, Aichi Medical University School of Medicine, Nagakute, Japan. · Division of Cancer Information and Control, Aichi Cancer Center Research Institute, Nagoya, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Clinical Research Center, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. · Department of Hepato-biliary-pancreatic Medicine, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. · Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center Hospital, Kanagawa, Japan. · Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan. · Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan. · Hokkaido Chitose College of Rehabilitation, Hokkaido, Japan. · Division of Hepatology and Pancreatology, Aichi Medical University School of Medicine, Nagakute, Japan. · Department of Public Health, Nagoya City University Graduate School of Medicine, Nagoya, Japan. · Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. ·PLoS One · Pubmed #30192808.

ABSTRACT: Genome-wide association studies (GWASs) have identified many single nucleotide polymorphisms (SNPs) that are significantly associated with pancreatic cancer susceptibility. We sought to replicate the associations of 61 GWAS-identified SNPs at 42 loci with pancreatic cancer in Japanese and to develop a risk model for the identification of individuals at high risk for pancreatic cancer development in the general Japanese population. The model was based on data including directly determined or imputed SNP genotypes for 664 pancreatic cancer case and 664 age- and sex-matched control subjects. Stepwise logistic regression uncovered five GWAS-identified SNPs at five loci that also showed significant associations in our case-control cohort. These five SNPs were included in the risk model and also applied to calculation of the polygenic risk score (PRS). The area under the curve determined with the leave-one-out cross-validation method was 0.63 (95% confidence interval, 0.60-0.66) or 0.61 (0.58-0.64) for versions of the model that did or did not include cigarette smoking and family history of pancreatic cancer in addition to the five SNPs, respectively. Individuals in the lowest and highest quintiles for the PRS had odds ratios of 0.62 (0.42-0.91) and 1.98 (1.42-2.76), respectively, for pancreatic cancer development compared with those in the middle quintile. We have thus developed a risk model for pancreatic cancer that showed moderately good discriminatory ability with regard to differentiation of pancreatic cancer patients from control individuals. Our findings suggest the potential utility of a risk model that incorporates replicated GWAS-identified SNPs and established demographic or environmental factors for the identification of individuals at increased risk for pancreatic cancer development.

22 Article Protocol digest of randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan clinical oncology group study (JCOG1407). 2018

Mizusawa, Junki / Fukutomi, Akira / Katayama, Hiroshi / Ishii, Hiroshi / Ioka, Tatsuya / Okusaka, Takuji / Ueno, Hideki / Ueno, Makoto / Ikeda, Masafumi / Mizuno, Nobumasa / Ozaka, Masato / Fukuda, Haruhiko / Furuse, Junji / Anonymous1620957. ·JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan. · Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan. Electronic address: a.fukutomi@scchr.jp. · Clinical Research Center, National Hospital Organization Shikoku Cancer Center, Shizuoka, Japan. · Department of Hepatobiliary and Pancreatic Oncology, Osaka International Cancer Institute, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Japan. · Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, Japan. · Department of Gastroenterology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Japan. · Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan. ·Pancreatology · Pubmed #30075908.

ABSTRACT: Gemcitabine is one of the standard treatments for locally advanced pancreatic cancer. Recent studies on metastatic pancreatic cancer have shown that combination chemotherapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP) prolonged the overall survival compared with gemcitabine alone. To select the most promising chemotherapy, a randomized phase II selection design trial was started in July 2016 to compare between modified FOLFIRINOX and GnP for patients with locally advanced pancreatic cancer. A total of 124 patients will be enrolled from 36 Japanese institutions within 2.5 years. The primary endpoint is the proportion of 1-year overall survival, and secondary endpoints are progression-free survival, distant metastasis-free survival, response rate in patients with target lesions, CA19-9 response, adverse events, treatment-related death, early death, grade 4 non-hematological toxicity, and dose intensity. This trial has been registered with the UMIN Clinical Trials Registry [http://www.umin.ac.jp/ctr/index.htm], and the registration number is UMIN000023143.

23 Article The Lymph Node Ratio Is an Independent Prognostic Factor in Pancreatic Cancer Patients Who Receive Curative Resection Followed by Adjuvant Chemotherapy. 2018

Aoyama, Toru / Yamamoto, Naoto / Kamiya, Mariko / Murakawa, Masaaki / Tamagawa, Hiroshi / Sawazaki, Sho / Numata, Masakatsu / Shiozawa, Manabu / Kobayashi, Satoshi / Ueno, Makoto / Morimoto, Manabu / Yukawa, Norio / Oshima, Takashi / Yoshikawa, Takaki / Rino, Yasushi / Masuda, Munetaka / Morinaga, Soichiro. ·Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan morinagas@kcch.jp aoyamat@yokohama-cu.ac.jp. · Department of Surgery, Yokohama City University, Yokohama, Japan. · Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan. · Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, Japan. ·Anticancer Res · Pubmed #30061263.

ABSTRACT: BACKGROUND/AIM: The present study investigated the impact of the lymph node ratio (LNR) on survival and recurrence in patients with pancreatic cancer after curative surgery followed by adjuvant chemotherapy. PATIENTS AND METHODS: This study included 189 patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer between 2005 and 2014. The risk factors for overall survival (OS) and recurrence-free survival (RFS) were identified. RESULTS: A lymph node ratio of 0.1 was considered to be the optimal cut-off point for classification based on the 3-year and 5-year survival rates. The OS rates at three and five years after surgery were 34.4% and 28.2% in the LNR <0.1 group, respectively, and 23.1% and 5.8% in the LNR ≥0.1 group, which amounted to a statistically significant difference (p=0.003). The RFS rates at one and three years after surgery were 26.6% and 20.5% in the LNR <0.1 group, respectively, and 8.0% and 0% in the LNR ≥0.1 group, which was a significant difference (p=0.001). A multivariate analysis demonstrated that the LNR was a significant independent risk factor for both the OS and RFS. CONCLUSION: The LNR was a risk factor for overall survival in patients who underwent curative surgery followed by adjuvant chemotherapy for pancreatic cancer. It is necessary to develop strategies to effectively utilize the lymph node metastasis status.

24 Article Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy. 2018

Shibuya, Hitoshi / Hijioka, Susumu / Sakamoto, Yasunari / Ito, Tetsuhide / Ueda, Keijiro / Komoto, Izumi / Kobayashi, Noritoshi / Kudo, Atsushi / Yasuda, Hiroaki / Miyake, Hayato / Arita, Junichi / Kiritani, Sho / Ikeda, Masafumi / Imaoka, Hiroshi / Ueno, Makoto / Kobayashi, Satoshi / Furuta, Mitsuhiro / Nagashio, Yoshikuni / Murohisa, Gou / Aoki, Taku / Matsumoto, Shigemi / Motoya, Masayo / Azemoto, Nobuaki / Itakura, Jun / Horiguchi, Shigeru / Yogi, Tatsuji / Kawagoe, Tetsuro / Miyaoka, Youichi / Imamura, Fumito / Senju, Michio / Arioka, Hitoshi / Hara, Kazuo / Imamura, Masayuki / Okusaka, Takuji. ·Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. shijioka@ncc.go.jp. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. shijioka@ncc.go.jp. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. · Neuroendocrine Tumor Center, Fukuoka Sanno Hospital, Fukuoka, Japan. · Internal University of Health and Welfare, Fukuoka, Japan. · Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Department of Surgery, Kansai Electric Power Hospital, Osaka, Japan. · Department of Oncology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan. · Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. · Division of Gastroenterology and Hepatology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. · Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, Japan. · Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Kanagawa, Japan. · Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan. · Department of Hepato-Biliary-Pancreatology, National Kyushu Cancer Center, Fukuoka, Japan. · Department of Gastroenterology, Seirei Hamamatsu General Hospital, Shizuoka, Japan. · Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan. · Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. · Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan. · Department of Gastroenterology, Shikoku Cancer Center, Matsuyama, Japan. · Department of Gastrointestinal, Breast and Endocrine Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. · Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan. · Department of Infectious, Respiratory, and Digestive Medicine, Control and Prevention of Infectious Diseases, Faculty of Medicine, University of the Ryukyu, Okinawa, Japan. · Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan. · Department of Endoscopy, Shimane Prefectural Central Hospital, Shimane, Japan. · Hitachi, Ltd., Hitachinaka General Hospital, Ibaraki, Japan. · Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. · Department of Medical Oncology, Yokohama Rosai Hospital, Kanagawa, Japan. ·Cancer Chemother Pharmacol · Pubmed #30054710.

ABSTRACT: PURPOSE: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. METHODS: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. RESULTS: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). CONCLUSIONS: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.

25 Article A randomised controlled trial of gemcitabine hydrochloride plus S-1 combination therapy versus gemcitabine hydrochloride therapy alone in pancreatic cancer patients aged ≥75 years: a study protocol for an open-label randomised feasibility study. 2018

Ishii, Hiroshi / Yamashita, Natsumi / Ueno, Makoto / Ohkawa, Shinichi / Saito, Akiko M / Sekimoto, Mitsugu. ·Clinical Research Center, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. · Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan. · Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan. · Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan. ·BMJ Open Gastroenterol · Pubmed #29527313.

ABSTRACT: Introduction: In Japan, the age of patients with pancreatic cancer has increased. Combination chemotherapies such as 5-fluorouracil/leucovorin, oxaliplatin and irinotecan therapy and gemcitabine hydrochloride (GEM) +nab paclitaxel therapy have been developed as the standard treatments for young patients with advanced recurrent pancreatic cancer. However, both therapies produce toxicity and their administration is limited by the patients' age or performance status. The efficacy and safety data obtained in the GEST study-a large-scale randomised controlled study conducted in patients with pancreatic cancer in Japan-suggested that GEM +S-1 (GS) combination therapy is a promising candidate for those aged between 75 and 80 years. However, for patients aged ≥80 years, no efficacy or safety data on GS therapy are currently available. Methods and analysis: This open-label, randomised phase II study will involve patients with advanced recurrent pancreatic cancer, aged ≥75 years, with favourable general conditions. Using the electronic data capture system, participants will be randomly allocated to groups with standard treatment (GEM therapy alone) and study treatment (GS therapy). The treatments will be administered until the conditions meet the discontinuation criteria. The primary endpoint is overall survival. Ethics and dissemination: This trial has been approved by the National Hospital Organisation's Central Review Board (H28-NHOD-01). Discussion: This study will reveal if GS therapy could be a standard treatment option for elderly patients with pancreatic cancer, by clarifying its efficacy and safety. Trial registration number: UMIN000025747; Pre-results.

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