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Pancreatic Neoplasms: HELP
Articles by Junji Furuse
Based on 49 articles published since 2008
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Between 2008 and 2019, J. Furuse wrote the following 49 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Clinical Practice Guidelines for Pancreatic Cancer 2016 From the Japan Pancreas Society: A Synopsis. 2017

Yamaguchi, Koji / Okusaka, Takuji / Shimizu, Kyoko / Furuse, Junji / Ito, Yoshinori / Hanada, Keiji / Shimosegawa, Tooru / Okazaki, Kazuichi / Anonymous7740903. ·From the *Clinic of Fukuoka Government Building, Hamanomachi Hospital, Fukuoka; †Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital; ‡Department of Gastroenterology, Tokyo Women's Medical University; §Department of Medical Oncology, Faculty of Medicine, Kyorin University; ∥Department of Radiation Oncology, National Cancer Center Hospital, Tokyo; ¶Department of Gastroenterology, JA Onomichi General Hospital, Onomichi; #Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai; and **Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Japan. ·Pancreas · Pubmed #28426492.

ABSTRACT: OBJECTIVES: Clinical Practice Guidelines for Pancreatic Cancer based on Evidence-Based Medicine 2006 were first published by the Japan Pancreas Society, and they were revised to Clinical Practice Guidelines for Pancreatic Cancer 2009 in July 2009 and were further revised to Clinical Practice Guidelines for Pancreatic Cancer 2013 in October 2013. These guidelines were established according to evidence-based medicine. In October 2016, the Clinical Practice Guidelines for Pancreatic Cancer were newly revised in Japanese. METHODS: In the revised version, we introduced the concepts of GRADE - grading recommendations assessment, development, and evaluation approach for better understanding of the current guidelines. RESULTS: The guidelines show algorithms for the diagnosis, treatment, and chemotherapy of pancreatic cancer and address 7 subjects: diagnosis, surgical therapy, adjuvant therapy, radiation therapy, chemotherapy, stent therapy, and palliative medicine. They include 51 clinical questions and 76 statements. There are statements corresponding to clinical questions, evidence levels, recommended strengths, and agreement rates. CONCLUSIONS: These guidelines represent the most standard clinical and practical management at this time in Japan. This is the English synopsis of the Clinical Practice Guidelines for Pancreatic Cancer 2016 in Japanese, which aims to disseminate the Japanese guidelines worldwide for the introduction of Japanese clinical management of these diseases.

2 Guideline EBM-based Clinical Guidelines for Pancreatic Cancer (2013) issued by the Japan Pancreas Society: a synopsis. 2014

Yamaguchi, Koji / Okusaka, Takuji / Shimizu, Kyoko / Furuse, Junji / Ito, Yoshinori / Hanada, Keiji / Shimosegawa, Tooru / Anonymous6910805. ·Department of Advanced Treatment of Pancreatic Diseases, School of Medicine, University of Occupational and Environmental Health, Kitakyushu yamaguch@med.uoeh-u.ac.jp. · Hepatobiliary and Pancreatic Oncology Division, National Cancer Center, Tokyo. · Department of Gastroenterology, Tokyo Women's Medical University, Tokyo. · Department of Internal Medicine, Medical Oncology, Kyorin University School of Medicine, Tokyo. · Department of Radiation Oncology, National Cancer Center, Tokyo. · Department of Gastroenterology, JA Onomichi General Hospital, Onomichi. · Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. ·Jpn J Clin Oncol · Pubmed #25205672.

ABSTRACT: Clinical practice guidelines for pancreatic cancer based on evidence-based medicine (2006) were published by the Japan Pancreas Society (Committee for revision of clinical guidelines for pancreatic cancer) in March 2009 in Japanese, revised to Clinical Practice Guidelines for Pancreatic Cancer based on evidence-based medicine (2009) in July 2009 in Japanese and further revised to Clinical Practice Guidelines for Pancreatic Cancer (2013) in October 2013 in Japanese. These guidelines were established according to evidence-based medicine. A total of 629 papers were collected from among 4612 reports concerning pancreatic cancer listed in PubMed and Igakuchuo Zasshi between May 2007 and January 2011. This new set of guidelines was written by members of the Committee for the Revision of Clinical Practice Guidelines for Pancreatic Cancer in the Japan Pancreas Society. The guidelines provide an algorithm for the diagnosis (Fig. 1) and treatment (Fig. 2) of pancreatic cancer and address six subjects (Diagnosis, Surgery, Adjuvant therapy, Radiation therapy, Chemotherapy and stent therapy), with 35 clinical questions and 57 recommendations.

3 Review Development of chemotherapy and significance of conversion surgery after chemotherapy in unresectable pancreatic cancer. 2018

Furuse, Junji / Shibahara, Junji / Sugiyama, Masanori. ·Faculty of Medicine, Department of Medical Oncology, Kyorin University, Tokyo, Japan. · Faculty of Medicine, Department of Pathology, Kyorin University, Tokyo, Japan. · Faculty of Medicine, Department of Surgery, Kyorin University, Tokyo, Japan. ·J Hepatobiliary Pancreat Sci · Pubmed #29651809.

ABSTRACT: While surgery currently remains the only potentially curative treatment available for pancreatic cancer, only 20% to 30% of patients have resectable disease at diagnosis. Recently, with the introduction of intensive chemotherapy regimens such as oxaliplatin, irinotecan, fluorouracil plus leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel, for the treatment of unresectable pancreatic cancer, the antitumor activity and overall survival in patients with pancreatic cancer have dramatically improved. These advances in intensive chemotherapy have led to the possibility of conversion of unresectable disease to resectable disease, and it has been reported that more than 20% of pancreatic cancer patients with unresectable locally advanced disease at diagnosis undergo successful conversion surgery after FOLFIRINOX therapy. In metastatic pancreatic cancer, resection for the primary lesion of pancreatic cancer may show some benefits for some patients with complete resolution of metastases by chemotherapy. Furthermore, surgical resection in some patients with only a few metastases, so-called oligometastases, have also been reported. Conversion surgery is becoming increasingly possible with the introduction of intensive chemotherapies, however, the actual clinical benefits of resection in such cases has not yet been sufficiently investigated. The long-term safety, feasibility and outcomes still need to be investigated in well-designed, multi-institutional studies on a large number of patients.

4 Review Emerging protein kinase inhibitors for treating pancreatic cancer. 2017

Furuse, Junji / Nagashima, Fumio. ·a Department of Medical Oncology , Kyorin University, Faculty of Medicine , Tokyo , Japan. ·Expert Opin Emerg Drugs · Pubmed #28253828.

ABSTRACT: INTRODUCTION: Pancreatic cancer, the incidence and mortality of which are increasing around the world, has the most dismal prognosis among the commonly encountered cancers. Systemic chemotherapy plays an important role in the treatment of patients with pancreatic cancer, and development of more effective chemotherapies is being sought. Areas covered: This review article provides a summary about protein kinase inhibitors that have been investigated for the treatment of pancreatic cancer, not only existing agents targeting RAS, EGFR, VEGFR, MEK, etc., but also various compounds targeting, including the MAPK, PI3 K/Akt/mTOR, and JAK/STAT signaling pathways, trials of which are currently ongoing. To date, none has shown sufficient efficacy as to merit becoming established as a standard treatment agent for pancreatic cancer. Expert opinion: As the toxicities of protein kinase inhibitors usually differ from those of cytotoxic agents, it could be of value to use these agents in combination with gemcitabine plus nab-paclitaxel. It may be reasonable to identify a suitable disease and/or predictive markers for new compounds in proof of concept trials. It is an urgent need to conduct phase III trials, on the basis of the results obtained, in subpopulations with biomarkers to predict the efficacy of these drugs.

5 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-

6 Review International Association of Pancreatology (IAP)/European Pancreatic Club (EPC) consensus review of guidelines for the treatment of pancreatic cancer. 2016

Takaori, Kyoichi / Bassi, Claudio / Biankin, Andrew / Brunner, Thomas B / Cataldo, Ivana / Campbell, Fiona / Cunningham, David / Falconi, Massimo / Frampton, Adam E / Furuse, Junji / Giovannini, Marc / Jackson, Richard / Nakamura, Akira / Nealon, William / Neoptolemos, John P / Real, Francisco X / Scarpa, Aldo / Sclafani, Francesco / Windsor, John A / Yamaguchi, Koji / Wolfgang, Christopher / Johnson, Colin D / Anonymous480853. ·Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: takaori@kuhp.kyoto-u.ac.jp. · Department of Surgery and Oncology, Pancreas Institute, University of Verona, Verona, Italy. · Academic Unit of Surgery, University of Glasgow, Glasgow, United Kingdom. · Department of Radiation Oncology, University Hospitals Freiburg, Germany. · Department of Pathology and Diagnostics, University of Verona, Verona, Italy. · Department of Pathology, Royal Liverpool University Hospital, Liverpool, United Kingdom. · Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom. · Pancreatic Surgery Unit, Università Vita e Salute, Milano, Italy. · HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, Hammersmith Hospital, London, United Kingdom. · Department of Medical Oncology, Kyorin University School of Medicine, Tokyo, Japan. · Endoscopic Unit, Paoli-Calmettes Institute, Marseille, France. · NIHR Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom. · Department of Radiation Oncology and Image-applied Therapy, Kyoto University Hospital, Kyoto, Japan. · Division of General Surgery, Yale University, New Haven, CT, United States of America. · Epithelial Carcinogenesis Group, CNIO-Spanish National Cancer Research Centre, Madrid, Spain. · Department of Surgery, University of Auckland, HBP/Upper GI Unit, Auckland City Hospital, Auckland, New Zealand. · Department of Advanced Treatment of Pancreatic Disease, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. · Department of Surgery, The Johns Hopkins University, Baltimore, MD, United States of America. · University Surgical Unit, Southampton General Hospital, Southampton, United Kingdom. ·Pancreatology · Pubmed #26699808.

ABSTRACT: BACKGROUND: Pancreatic cancer is one of the most devastating diseases with an extremely high mortality. Medical organizations and scientific societies have published a number of guidelines to address active treatment of pancreatic cancer. The aim of this consensus review was to identify where there is agreement or disagreement among the existing guidelines and to help define the gaps for future studies. METHODS: A panel of expert pancreatologists gathered at the 46th European Pancreatic Club Meeting combined with the 18th International Association of Pancreatology Meeting and collaborated on critical reviews of eight English language guidelines for the clinical management of pancreatic cancer. Clinical questions (CQs) of interest were proposed by specialists in each of nine areas. The recommendations for the CQs in existing guidelines, as well as the evidence on which these were based, were reviewed and compared. The evidence was graded as sufficient, mediocre or poor/absent. RESULTS: Only 4 of the 36 CQs, had sufficient evidence for agreement. There was also agreement in five additional CQs despite the lack of sufficient evidence. In 22 CQs, there was disagreement regardless of the presence or absence of evidence. There were five CQs that were not addressed adequately by existing guidelines. CONCLUSION: The existing guidelines provide both evidence- and consensus-based recommendations. There is also considerable disagreement about the recommendations in part due to the lack of high level evidence. Improving the clinical management of patients with pancreatic cancer, will require continuing efforts to undertake research that will provide sufficient evidence to allow agreement.

7 Review [Current status and future directions of chemotherapy for pancreatic cancer]. 2013

Furuse, Junji. ·Department of Medical Oncology, Kyorin University School of Medicine. ·Nihon Shokakibyo Gakkai Zasshi · Pubmed #24305093.

ABSTRACT: -- No abstract --

8 Review The Hepatobiliary and Pancreatic Oncology (HBPO) Group of the Japan Clinical Oncology Group (JCOG): history and future direction. 2013

Furuse, Junji / Ishii, Hiroshi / Okusaka, Takuji. ·Department of Internal Medicine, Medical Oncology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo 181-8611, Japan. jfuruse@ks.kyorin-u.ac.jp ·Jpn J Clin Oncol · Pubmed #23100604.

ABSTRACT: The Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG) was constituted in April 2008 to develop new standard treatments for hepatobiliary and pancreatic cancer. In pancreatic cancer, the Hepatobiliary and Pancreatic Oncology Group focuses on establishing standard chemotherapy or chemoradiotherapy for unresectable locally advanced disease. The JCOG 0506 study was a Phase II study of gemcitabine alone to examine its efficacy and safety in patients with locally advanced disease. The results in survival significantly exceeded expectations, and gemcitabine monotherapy has come to be regarded as the provisional standard therapy by our group. Following JCOG 0506, the JCOG 1106 study, which is currently under investigation, is a randomized Phase II study to evaluate the efficacy of induction chemotherapy with gemcitabine in combination with S-1 chemoradiotherapy and select a candidate therapeutic agent in a Phase III study comparing with gemcitabine alone. The JCOG 0805 study was a randomized Phase II study comparing S-1 monotherapy with gemcitabine plus S-1 combination therapy for unresectable biliary tract cancer. As a result, gemcitabine plus S-1 combination therapy was considered the more promising candidate in comparison with the gemcitabine plus cisplatin combination therapy in a subsequent Phase III trial. The Hepatobiliary and Pancreatic Oncology Group is planning a Phase III study to compare gemcitabine plus S-1 combination therapy with gemcitabine plus cisplatin combination therapy (JCOG PC1113 study). No standard postoperative adjuvant treatment has been established. We plan to conduct a Phase III study to compare S-1 as adjuvant therapy after surgery with surgery alone in patients with biliary tract cancer (JCOG PC1202).

9 Review [Frontier of chemotherapy of pancreatic cancer]. 2010

Furuse, Junji. · ·Nihon Naika Gakkai Zasshi · Pubmed #20578369.

ABSTRACT: -- No abstract --

10 Review Current status of chemoradiotherapy for locally advanced pancreatic cancer in Japan. 2008

Okusaka, Takuji / Ito, Yoshinori / Furuse, Junji / Yamada, Shigeru / Ishii, Hiroshi / Shibuya, Keiko / Ioka, Tatsuya / Shinchi, Hiroyuki. ·Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. tokusaka@ncc.go.jp ·Int J Clin Oncol · Pubmed #18463956.

ABSTRACT: Although the results of randomized controlled trials for locally advanced pancreatic cancer conducted between 1969 and 1988 demonstrated a survival advantage for concurrent radiotherapy and bolus 5-fluorouracil (FU) injection, the prognosis of patients with this disease remains very poor. In an attempt to improve patient outcome after chemoradiotherapy, various clinical trials for this disease have been conducted in Japan. These trials were designed to evaluate novel chemotherapy regimens combined with conventional radiotherapy, or intensive radiotherapy in combination with chemotherapy. After gemictabine was shown to yield a better survival outcome than 5-FU in patients with advanced disease, this drug was investigated as a chemotherapeutic agent and/or radiosensitizer for locally advanced pancreatic cancer in a number of trials. S-1, a novel oral fluoropyrimidine derivative that appears promising for the treatment of metastatic disease, is also being intensively evaluated in Japan for the treatment of locally advanced pancreatic cancer. In this review, we summarize recent treatment strategies that are being used in Japan with the goal of establishing a new standard therapy for locally advanced pancreatic cancer.

11 Clinical Trial Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05). 2019

Motoi, Fuyuhiko / Kosuge, Tomoo / Ueno, Hideki / Yamaue, Hiroki / Satoi, Sohei / Sho, Masayuki / Honda, Goro / Matsumoto, Ippei / Wada, Keita / Furuse, Junji / Matsuyama, Yutaka / Unno, Michiaki / Anonymous1391083. ·Department of Surgery, Tohoku University School of Medicine, Sendai, Japan. · Hepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Tokyo, Japan. · Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan. · Second Department of Surgery, Wakayama Medical University, Wakayama, Japan. · Department of Surgery, Kansai Medical University, Osaka, Japan. · Department of Surgery, Nara Medical University, Nara, Japan. · Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan. · Department of Surgery, Kindai University Faculty of Medicine, Osaka, Japan. · Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan. · Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan. · Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan. ·Jpn J Clin Oncol · Pubmed #30608598.

ABSTRACT: A randomized, controlled trial has begun to compare neoadjuvant chemotherapy using gemcitabine and S-1 with upfront surgery for patients planned resection of pancreatic cancer. Patients were enrolled after the diagnosis of resectable or borderline resectable by portal vein involvement pancreatic cancer with histological confirmation. They were randomly assigned to either neoadjuvant chemotherapy or upfront surgery. Adjuvant chemotherapy using S-1 was administered for 6 months to patients with curative resection who fully recovered within 10 weeks after surgery in both arms. The primary endpoint is overall survival; secondary endpoints include adverse events, resection rate, recurrence-free survival, residual tumor status, nodal metastases and tumor marker kinetics. The target sample size was required to be at least 163 (alpha-error 0.05; power 0.8) in both arms. A total of 360 patients were required after considering ineligible cases. This trial began in January 2013 and was registered with the UMIN Clinical Trials Registry (UMIN000009634).

12 Clinical Trial A randomized Phase III trial of adjuvant S-1 therapy vs. observation alone in resected biliary tract cancer: Japan Clinical Oncology Group Study (JCOG1202, ASCOT). 2018

Nakachi, Kohei / Konishi, Masaru / Ikeda, Masafumi / Mizusawa, Junki / Eba, Junko / Okusaka, Takuji / Ishii, Hiroshi / Fukuda, Haruhiko / Furuse, Junji / Anonymous5930937. ·Department of Gastroenterology, Otaru General Hospital, Otaru. · Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Kashiwa. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa. · JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo. · Clinical Research Center, National Hospital Organization Shikoku Cancer Center, Matsuyama. · Department of Medical Oncology, Kyorin University School of Medicine, Tokyo, Japan. ·Jpn J Clin Oncol · Pubmed #29462482.

ABSTRACT: No standard adjuvant treatment has been established for patients with curatively resected biliary tract cancer. S-1 has been reported to show promising efficacy with mild toxicity profiles in patients with advanced biliary tract cancer, and adjuvant S-1 therapy has been demonstrated to provide survival benefit in patients with resected gastric cancer and pancreatic cancer. The aim of this open-label, multicenter, randomized Phase III trial is to confirm that adjuvant chemotherapy with S-1 would prolong overall survival in patients with resected biliary tract cancer. This study was activated in September 2013. A total of 350 patients planned to be enrolled from 36 Japanese institutions over a period of 4 years. At July 2017, the protocol was revised to increase power from 70% to 80%. Therefore, the planned total sample size is 440. The primary endpoint is overall survival. This trial is registered with the UMIN Clinical Trials Registry as UMIN000011688.

13 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.

14 Clinical Trial Updated results from GEST study: a randomized, three-arm phase III study for advanced pancreatic cancer. 2017

Okusaka, Takuji / Miyakawa, H / Fujii, H / Nakamori, S / Satoh, T / Hamamoto, Y / Ito, T / Maguchi, H / Matsumoto, S / Ueno, H / Ioka, T / Boku, N / Egawa, S / Hatori, T / Furuse, J / Mizumoto, K / Ohkawa, S / Yamaguchi, T / Yamao, K / Funakoshi, A / Chen, J S / Cheng, A L / Sato, A / Ohashi, Y / Tanaka, M / Anonymous450897. ·Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. tokusaka@ncc.go.jp. · Division of Biliopancreatology, Sapporo Kosei General Hospital, Sapporo, Japan. · Division of Clinical Oncology, Jichi Medical University, Tochigi, Japan. · Hepato-Biliary-Pancreatic Surgery, Osaka National Hospital, Osaka, Japan. · Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Japan. · Keio Cancer Center, Keio University Hospital, Tokyo, Japan. · Department of Medicine and Bioreguratory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. · Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan. · Department of Medical Oncology, Kyoto University Hospital, Kyoto, Japan. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. · Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. · Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan. · Department of Surgery, Tohoku University, Sendai, Japan. · Department of Surgery and Digestive Diseases Center, International University of Health and Welfare Mita Hospital, Tokyo, Japan. · Department of Medical Oncology, Kyorin University School of Medicine, Tokyo, Japan. · Kyushu University Hospital Cancer Center, Fukuoka, Japan. · Division of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, Japan. · Department of Gastroenterology, Chiba Cancer Center, Chiba, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan. · Division of Pancreatology, Fukuoka Sanno Hospital, Fukuoka, Japan. · Division of Hematology-Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Tao-Yuan, Taiwan, Republic of China. · Department of Oncology, National Taiwan University Hospital, and National Taiwan University Cancer Center, Taipei, Taiwan, Republic of China. · Department of Medical Oncology, Hirosaki University Graduate School of Medicine, Aomori, Japan. · Department of Integrated Science and Engineering for Sustainable Society, Chuo University, Tokyo, Japan. · Department of Surgery, Shimonoseki City Hospital, Shimonoseki, Japan. ·J Cancer Res Clin Oncol · Pubmed #28210843.

ABSTRACT: PURPOSE: The GEST study showed non-inferiority of S-1 but not superiority of gemcitabine plus S-1 (GS) to gemcitabine alone for overall survival with the data by the cut-off date of 31st July in 2010 for chemo-naïve patients with advanced pancreatic cancer. We considered it important to determine whether S-1 maintains non-inferiority after a long-term follow-up in the GEST study and to obtain a firm positive conclusion. In addition, it may be an interesting challenge to explore the efficacious profile of GS in the long-term follow-up study. Using the data from the follow-up period, background and efficacy in patients from Taiwan and Japan, as well as the rates of tumor shrinkage in locally advanced and metastatic patients (Waterfall plot) were also analyzed. METHODS: The results of the primary analysis were reconfirmed, and subset analysis of overall survival and progression-free survival was performed based on the overall survival data updated by the cut-off date of 31st July in 2011. RESULTS: The median follow-up period was 29.8 months, and 795 deaths occurred (95.6%). The median overall survival was 8.8 months for gemcitabine, 9.7 months for S-1 (hazard ratio [HR], 0.96; 97.5% confidence interval [CI], 0.79-1.17), and 9.9 months for GS (HR 0.91; 97.5% CI 0.75-1.11). In patients with performance status (PS) 0, the median overall survival was 9.8 months for gemcitabine, 10.9 months for S-1, and 10.5 months for GS. In patients with PS 1, the median overall survival was 6.2 months for gemcitabine, 6.3 months for S-1, and 9.6 months for GS. CONCLUSION: Our survey reconfirmed the non-inferiority of S-1 to gemcitabine and showed S-1 can be used as one of the standard treatment options for advanced pancreatic cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00498225.

15 Clinical Trial Randomised phase II trial of irinotecan plus S-1 in patients with gemcitabine-refractory pancreatic cancer. 2017

Ioka, T / Komatsu, Y / Mizuno, N / Tsuji, A / Ohkawa, S / Tanaka, M / Iguchi, H / Ishiguro, A / Kitano, M / Satoh, T / Yamaguchi, T / Takeda, K / Kida, M / Eguchi, K / Ito, T / Munakata, M / Itoi, T / Furuse, J / Hamada, C / Sakata, Y. ·Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511, Japan. · Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, 5-chome, Kita 14 Jou Nishi, Kita-ku, Sapporo 060-8648, Japan. · Department of Gastroenterology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. · Department of Medical Oncology, Kochi Health Sciences Center, 2125-1 Ike, Kochi 781-0111, Japan. · Department of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center Hospital, 2-3-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan. · Department of Surgery and Oncology, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. · Department of Gastroenterology, National Hospital Organization Shikoku Cancer Center, 160 Kou, Minamiumemoto-chou, Matsuyama 791-0280, Japan. · Department of Medical Oncology, Hirosaki University, 53 Hon-cho, Hirosaki 036-8562, Japan. · Department of Gastroenterology and Hepatology, Kinki University School of Medicine, 377-2 Onohigashi, Osakasayama 589-8511, Japan. · Faculty of Medicine, Department of Medical Oncology, Kinki University, 377-2 Onohigashi, Osakasayama 589-8511, Japan. · Division of Gastroenterology, Chiba Cancer Center Hospital, 666-2 Nitona-cho, Chuo-ku, Chiba 260-8717, Japan. · Department of Clinical Oncology, Osaka City General Hospital, 2-13-22 Miyakojima-hondori, Miyakojia-ku, Osaka 534-0021, Japan. · Department of Medicine, Kitasato University School of Medicine, 2-1-1 Asamizodai, Minami-ku, Sagamihara 252-0374, Japan. · Department of Internal Medicine, Medical Oncology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-Ku, Tokyo 173-8605, Japan. · Department of Medicine and Bioregulatory Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. · Department of Medical Oncology, Misawa City Hospital, 164-65 Oazamisawaazahoriuchi, Misawa 033-0022, Japan. · Department of Gastroenterological Medicine, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 166-0023, Japan. · Department of Medical Oncology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, 181-8611, Japan. · Faculty of Engineering, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan. ·Br J Cancer · Pubmed #28081543.

ABSTRACT: BACKGROUND: We aimed to compare the efficacy and safety of irinotecan/S-1 (IRIS) therapy with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer. METHODS: Patients were treated with oral S-1 (80-120 mg for 14 days every 4 weeks) plus intravenous irinotecan (100 mg m RESULTS: Of 137 patients enrolled, 127 were eligible for efficacy. The median PFS in the IRIS group and S-1 monotherapy group were 3.5 and 1.9 months, respectively (hazard ratio (HR)=0.77; 95% confidence interval (CI), 0.53-1.11; P=0.18), while the median overall survival (OS) were 6.8 and 5.8 months, respectively (HR=0.75; 95% CI, 0.51-1.09; P=0.13). Response rate was significantly higher in the IRIS group than in the S-1 monotherapy group (18.3% vs 6.0%, P=0.03). Grade 3 or higher neutropenia and anorexia occurred more frequently in the IRIS group. CONCLUSIONS: There was a trend for better PFS and OS in the IRIS group that could be a treatment arm in the clinical trials for gemcitabine-refractory pancreatic cancer.

16 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.

17 Clinical Trial A randomized phase II study of S-1 plus oral leucovorin versus S-1 monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer. 2016

Ueno, M / Okusaka, T / Omuro, Y / Isayama, H / Fukutomi, A / Ikeda, M / Mizuno, N / Fukuzawa, K / Furukawa, M / Iguchi, H / Sugimori, K / Furuse, J / Shimada, K / Ioka, T / Nakamori, S / Baba, H / Komatsu, Y / Takeuchi, M / Hyodo, I / Boku, N. ·Division of Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center, Yokohama uenom@kcch.jp. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo. · Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo. · Department of Gastroenterology, The University of Tokyo, Graduate School of Medicine, Tokyo. · Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa. · Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya. · Department of Surgery, Oita Red Cross Hospital, Oita. · Department of Gastroenterology, National Kyushu Cancer Center, Fukuoka. · Department of Gastroenterology, National Hospital Organization Shikoku Cancer Center, Matsuyama. · Gastroenterological Center, Yokohama City University Medical Center, Yokohama. · Department of Medical Oncology, Kyorin University School of Medicine, Tokyo. · Department of Medical Oncology, Saitama Medical University International Medical Center, Saitama. · Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka. · Hepato-biliary-pancreatic Surgery, National Hospital Organization Osaka National Hospital, Osaka. · Department of Gastroenterological Surgery, Kumamoto University, Kumamoto. · Department of Cancer Chemotherapy, Hokkaido University Hospital Cancer Center, Sapporo. · Department of Clinical Medicine (Biostatistics and Pharmaceutical Medicine), Kitasato University School of Pharmacy, Tokyo. · Division of Gastroenterology, University of Tsukuba, Tsukuba. · Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Japan. ·Ann Oncol · Pubmed #26681680.

ABSTRACT: BACKGROUND: We evaluated the efficacy and toxicity of adding oral leucovorin (LV) to S-1 when compared with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer (PC). PATIENTS AND METHODS: Gemcitabine-refractory PC patients were randomly assigned in a 1:1 ratio to receive S-1 at 40, 50, or 60 mg according to body surface area plus LV 25 mg, both given orally twice daily for 1 week, repeated every 2 weeks (SL group), or S-1 monotherapy at the same dose as the SL group for 4 weeks, repeated every 6 weeks (S-1 group). The primary end point was progression-free survival (PFS). RESULTS: Among 142 patients enrolled, 140 were eligible for efficacy assessment (SL: n = 69 and S-1: n = 71). PFS was significantly longer in the SL group than in the S-1 group [median PFS, 3.8 versus 2.7 months; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.37-0.85; P = 0.003]). The disease control rate was significantly higher in the SL group than in the S-1 group (91% versus 72%; P = 0.004). Overall survival (OS) was similar in both groups (median OS, 6.3 versus 6.1 months; HR, 0.82; 95% CI, 0.54-1.22; P = 0.463). After adjusting for patient background factors in a multivariate analysis, OS tended to be better in the SL group (HR, 0.71; 95% CI, 0.47-1.07; P = 0.099). Both treatments were well tolerated, although gastrointestinal toxicities were slightly more severe in the SL group. CONCLUSION: The addition of LV to S-1 significantly improved PFS in patients with gemcitabine-refractory advanced PC, and a phase III trial has been initiated in a similar setting. CLINICAL TRIALS NUMBER: Japan Pharmaceutical Information Center: JapicCTI-111554.

18 Clinical Trial A phase I/Ib study of trametinib (GSK1120212) alone and in combination with gemcitabine in Japanese patients with advanced solid tumors. 2015

Kasuga, Akiyoshi / Nakagawa, Kazuhiko / Nagashima, Fumio / Shimizu, Toshio / Naruge, Daisuke / Nishina, Shinichi / Kitamura, Hiroshi / Kurata, Takayasu / Takasu, Atsuko / Fujisaka, Yasuhito / Okamoto, Wataru / Nishimura, Yuichiro / Mukaiyama, Akihira / Matsushita, Hideki / Furuse, Junji. ·Department of Medical Oncology, Kyorin University Hospital, 6-20-2 Shinkawa, 181-8611, Mitaka, Tokyo, Japan. · Department of Medical Oncology, Faculty of Medicine, Kinki University Hospital, 377-2, Ono-Higashi, 577-0818, Osakasayama City, Osaka, Japan. · Medicines Development, Oncology Therapeutic Area, GlaxoSmithKline K.K., 6-15, Sendagaya 4-chome, 151-8566, Tokyo, Japan. · Department of Medical Oncology, Kyorin University Hospital, 6-20-2 Shinkawa, 181-8611, Mitaka, Tokyo, Japan. jfuruse@ks.kyorin-u.ac.jp. ·Invest New Drugs · Pubmed #26259955.

ABSTRACT: BACKGROUND: Trametinib is an inhibitor of MEK1/MEK2 activation and kinase activity. In order to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of single-agent trametinib (part 1) and trametinib in combination with gemcitabine (part 2), we undertook the first clinical study of this combination in Japanese patients with cancer and herein report our results. METHODS: In part 1, 13 patients with advanced solid tumors were enrolled into 3 dose cohorts, receiving trametinib once daily at a dose of 1.0, 2.0, or 3.0 mg. In part 2, 5 patients with pancreatic cancer received trametinib (2.0 mg once daily) in combination with gemcitabine (1000 mg/m(2)). RESULTS: In part 1, a dose-limiting toxicity was observed in a patient in the 2.0-mg dose cohort, but the maximum tolerated dose was not reached at doses up to 3.0 mg daily. The best overall response was a PR in 1 patient, and 6 patients had SD. In part 2, the combination of trametinib and gemcitabine was tolerated for a short period of time. However, serious interstitial lung disease (ILD) was observed in 3 of 5 patients 4 weeks or more after the start of the treatment, including 1 fatal case. Three patients achieved a PR, and 2 patients had SD. The most common adverse event was rash (85 % in part 1 and 100 % in part 2). CONCLUSIONS: Trametinib monotherapy was tolerable in Japanese patients with cancer. However, the combination of trametinib plus gemcitabine carried a higher risk as compared with monotherapy, during which no ILD was observed. (ClinicalTrials.gov number, NCT01324258.).

19 Clinical Trial Efficacy and safety of axitinib in combination with gemcitabine in advanced pancreatic cancer: subgroup analyses by region, including Japan, from the global randomized Phase III trial. 2015

Ioka, Tatsuya / Okusaka, Takuji / Ohkawa, Shinichi / Boku, Narikazu / Sawaki, Akira / Fujii, Yosuke / Kamei, Yoichi / Takahashi, Satori / Namazu, Katsushi / Umeyama, Yoshiko / Bycott, Paul / Furuse, Junji. ·Department of Hepatobiliary and Pancreatic Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka ioka-ta@mc.pref.osaka.jp. · Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo. · Department of Gastroenterology, Kanagawa Cancer Center, Kanagawa. · Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka. · Department of Clinical Oncology, Kawasaki Medical School, Okayama. · Pfizer Japan Inc., Tokyo, Japan. · Pfizer Oncology, San Diego, CA, USA. · Department of Medical Oncology, Kyorin University School of Medicine, Tokyo, Japan. ·Jpn J Clin Oncol · Pubmed #25647781.

ABSTRACT: OBJECTIVE: Axitinib is a potent and selective inhibitor of vascular endothelial growth factor receptors 1-3. This analysis compared efficacy and safety of axitinib plus gemcitabine in patients with advanced pancreatic cancer from Japan, North America and the European Union, enrolled in a randomized Phase III study. METHODS: Patients (n = 632), stratified by disease extent, were randomly assigned (1:1) to receive axitinib/gemcitabine or placebo/gemcitabine. Axitinib was administered at a starting dose of 5 mg orally twice daily and gemcitabine at 1000 mg/m(2) once weekly for 3 weeks in 4 week cycles. Primary endpoint was overall survival. RESULTS: Among Japanese patients, median overall survival was not estimable (95% confidence interval, 7.4 months-not estimable) with axitinib/gemcitabine (n = 58) and 9.9 months (95% confidence interval, 7.4-10.5) with placebo/gemcitabine (n = 56) (hazard ratio 1.093 [95% confidence interval, 0.525-2.274]). Median survival follow-up (range) was 5.1 months (0.02-12.3) with axitinib/gemcitabine vs. 5.4 months (1.8-10.5) with placebo/gemcitabine. Similarly, no difference was detected in overall survival between axitinib/gemcitabine and placebo/gemcitabine in patients from North America or the European Union. Common adverse events with axitinib/gemcitabine in Japanese patients were fatigue, anorexia, dysphonia, nausea and decreased platelet count. Axitinib safety profile was generally similar in patients from the three regions, although there were differences in incidence of some adverse events. An exploratory analysis did not show any correlation between axitinib/gemcitabine-related hypertension and overall survival. CONCLUSIONS: Axitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions.

20 Clinical Trial Phase II study of FOLFIRINOX for chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. 2014

Okusaka, Takuji / Ikeda, Masafumi / Fukutomi, Akira / Ioka, Tatsuya / Furuse, Junji / Ohkawa, Shinichi / Isayama, Hiroyuki / Boku, Narikazu. ·Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. ·Cancer Sci · Pubmed #25117729.

ABSTRACT: The FOLFIRINOX combination of chemotherapy drugs had not been fully evaluated for Japanese pancreatic cancer patients. Therefore, we carried out a phase II study to examine the efficacy and safety of FOLFIRINOX in chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. FOLFIRINOX (i.v. infusion of 85 mg/m(2) oxaliplatin, 180 mg/m(2) irinotecan, and 200 mg/m(2) l-leucovorin, followed by a bolus of 400 mg/m(2) fluorouracil and a 46-h continuous infusion of 2400 mg/m(2) fluorouracil) was given every 2 weeks. The primary endpoint was the response rate. The 36 enrolled patients received a median of eight (range, 1-25) treatment cycles. The response rate was 38.9% (95% confidence interval [CI], 23.1-56.5); median overall survival, 10.7 months (95% CI, 6.9-13.2); and median progression-free survival, 5.6 months (95% CI, 3.0-7.8). Major grade 3 or 4 toxicities included neutropenia (77.8%), febrile neutropenia (22.2%), thrombocytopenia (11.1%), anemia (11.1%), anorexia (11.1%), diarrhea (8.3%), nausea (8.3%), elevated alanine aminotransferase levels (8.3%), and peripheral sensory neuropathy (5.6%). Febrile neutropenia occurred only during the first cycle. There were no treatment-related deaths. FOLFIRINOX can be a standard regimen showing favorable efficacy and acceptable toxicity profile in chemotherapy-naïve Japanese patients with metastatic pancreatic cancer.

21 Clinical Trial Serum levels of IL-6 and IL-1β can predict the efficacy of gemcitabine in patients with advanced pancreatic cancer. 2013

Mitsunaga, S / Ikeda, M / Shimizu, S / Ohno, I / Furuse, J / Inagaki, M / Higashi, S / Kato, H / Terao, K / Ochiai, A. ·Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. smitsuna@east.ncc.go.jp ·Br J Cancer · Pubmed #23591198.

ABSTRACT: BACKGROUND: With this study, we sought to characterise the impact of pro-inflammatory cytokines on the outcomes of gemcitabine monotherapy (GEM) in patients with pancreatic cancer (PC). METHODS: Treatment-naive patients with advanced PC and no obvious infections were eligible for enrolment. All of the patients were scheduled to undergo systemic chemotherapy. Serum pro-inflammatory cytokines were measured using an electro-chemiluminescence assay method before chemotherapy. High cytokine levels were defined as values greater than the median. Clinical data were collected prospectively. RESULTS: Sixty patients who received GEM were included in the analysis. High IL-6 and IL-1β levels were poor prognostic factors for overall survival in a multivariate analysis (P=0.011 and P=0.048, respectively). Patients with both a high IL-6 level and a high IL-1β level exhibited shortened overall and progression-free survival, a reduction in the tumour control rate, and a high dose intensity of GEM compared with patients with low levels of both IL-6 and IL-1β. CONCLUSION: The serum levels of IL-6 and IL-1β predict the efficacy of GEM in patients with advanced PC.

22 Clinical Trial Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. 2013

Ueno, Hideki / Ioka, Tatsuya / Ikeda, Masafumi / Ohkawa, Shinichi / Yanagimoto, Hiroaki / Boku, Narikazu / Fukutomi, Akira / Sugimori, Kazuya / Baba, Hideo / Yamao, Kenji / Shimamura, Tomotaka / Sho, Masayuki / Kitano, Masayuki / Cheng, Ann-Lii / Mizumoto, Kazuhiro / Chen, Jen-Shi / Furuse, Junji / Funakoshi, Akihiro / Hatori, Takashi / Yamaguchi, Taketo / Egawa, Shinichi / Sato, Atsushi / Ohashi, Yasuo / Okusaka, Takuji / Tanaka, Masao. ·Taiho Pharmaceutical, Tokyo, Japan. ·J Clin Oncol · Pubmed #23547081.

ABSTRACT: PURPOSE: The present phase III study was designed to investigate the noninferiority of S-1 alone and superiority of gemcitabine plus S-1 compared with gemcitabine alone with respect to overall survival. PATIENTS AND METHODS: The participants were chemotherapy-naive patients with locally advanced or metastatic pancreatic cancer. Patients were randomly assigned to receive only gemcitabine (1,000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle), only S-1 (80, 100, or 120 mg/d according to body-surface area on days 1 through 28 of a 42-day cycle), or gemcitabine plus S-1 (gemcitabine 1,000 mg/m(2) on days 1 and 8 plus S-1 60, 80, or 100 mg/d according to body-surface area on days 1 through 14 of a 21-day cycle). RESULTS: In the total of 834 enrolled patients, median overall survival was 8.8 months in the gemcitabine group, 9.7 months in the S-1 group, and 10.1 months in the gemcitabine plus S-1 group. The noninferiority of S-1 to gemcitabine was demonstrated (hazard ratio, 0.96; 97.5% CI, 0.78 to 1.18; P < .001 for noninferiority), whereas the superiority of gemcitabine plus S-1 was not (hazard ratio, 0.88; 97.5% CI, 0.71 to 1.08; P = .15). All treatments were generally well tolerated, although hematologic and GI toxicities were more severe in the gemcitabine plus S-1 group than in the gemcitabine group. CONCLUSION: Monotherapy with S-1 demonstrated noninferiority to gemcitabine in overall survival with good tolerability and presents a convenient oral alternative for locally advanced and metastatic pancreatic cancer.

23 Clinical Trial A multicenter phase II trial of S-1 with concurrent radiation therapy for locally advanced pancreatic cancer. 2013

Ikeda, Masafumi / Ioka, Tatsuya / Ito, Yoshinori / Yonemoto, Naohiro / Nagase, Michitaka / Yamao, Kenji / Miyakawa, Hiroyuki / Ishii, Hiroshi / Furuse, Junji / Sato, Keiko / Sato, Tosiya / Okusaka, Takuji. ·Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Chiba, Japan. masikeda@east.ncc.go.jp ·Int J Radiat Oncol Biol Phys · Pubmed #22677367.

ABSTRACT: PURPOSE: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). METHODS AND MATERIALS: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m2 twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m2/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. RESULTS: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of ≥100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. CONCLUSIONS: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

24 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.

25 Clinical Trial Multicenter phase II study of gemcitabine and S-1 combination therapy (GS Therapy) in patients with metastatic pancreatic cancer. 2011

Ueno, Hideki / Okusaka, Takuji / Furuse, Junji / Yamao, Kenji / Funakoshi, Akihiro / Boku, Narikazu / Ohkawa, Shinichi / Yokosuka, Osamu / Tanaka, Katsuaki / Moriyasu, Fuminori / Nakamori, Shoji / Sato, Tosiya. ·Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. hiueno@ncc.go.jp ·Jpn J Clin Oncol · Pubmed #21715364.

ABSTRACT: OBJECTIVE: The aim of this multicenter Phase II study was to assess the efficacy and toxicity of gemcitabine and S-1 combination therapy for metastatic pancreatic cancer. METHODS: Chemotherapy-naïve patients with histologically or cytologically proven metastatic pancreatic adenocarcinoma were eligible for this study. Gemcitabine was administered at a dose of 1000 mg/m(2) over 30 min on days 1 and 8, and oral S-1 at a dose of 40 mg/m(2) twice daily from days 1 to 14, repeated every 3 weeks. RESULTS: A total of 55 patients were included and the efficacy and toxicity were analyzed in 54 patients who received at least one dose of gemcitabine and S-1 combination therapy. Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44.4% (95% confidence interval: 30.9-58.6%). The median progression-free survival was 5.9 months (95% confidence interval: 4.1-6.9 months) and the median overall survival was 10.1 months (95% confidence interval: 8.5-10.8 months) with a 1-year survival rate of 33.0%. The major Grade 3-4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%) and rash (7%). Hematological toxicity was mostly transient and there was only one episode of febrile neutropenia ≥Grade 3. CONCLUSIONS: Gemcitabine and S-1 combination therapy produced a high response rate with good survival in patients with metastatic pancreatic cancer. A randomized Phase III study to confirm the efficacy of gemcitabine and S-1 combination therapy is ongoing.

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