{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T18:50:06Z","timestamp":1740163806757,"version":"3.37.3"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Cancer Center Research and Development Fund","award":["grant numbers 23-A-22","26-A-4","29-A-3","2020-J-3"],"award-info":[{"award-number":["grant numbers 23-A-22","26-A-4","29-A-3","2020-J-3"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["grant numbers JP16ck0106079","JP19ck0106350"],"award-info":[{"award-number":["grant numbers JP16ck0106079","JP19ck0106350"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health, Labour and Welfare of Japan","award":["Grant-in-Aid for Clinical Cancer Research (H22-ganrinsho-ippan-013)"],"award-info":[{"award-number":["Grant-in-Aid for Clinical Cancer Research (H22-ganrinsho-ippan-013)"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>JCOG1113 is a randomized phase III trial in patients with advanced biliary tract cancers (BTCs) (UMIN000001685), and gemcitabine plus S-1 (GS) was not inferior to gemcitabine plus cisplatin (GC). However, poor renal function often results in high toxicity of S-1. Therefore, we examined whether GS can be recommended for patients with low creatinine clearance (CCr). Renal function was classified by CCr as calculated by the Cockcroft-Gault formula: high CCr (CCr\u2009\u2265\u200980\u00a0ml\/min) and low CCr (80\u2009&gt;\u2009CCr\u2009\u2265\u200950\u00a0ml\/min). Of 354 patients, 87 patients on GC and 91 on GS were included in the low CCr group, while there were 88 patients on GC and 88 patients on GS in the high CCr group. The HR of overall survival for GS compared with GC was 0.687 (95% CI 0.504\u20130.937) in the low CCr group. Although the total number of incidences of all Grade 3\u20134 non-haematological adverse reactions was higher (36.0% vs. 11.8%, <jats:italic>p<\/jats:italic>\u2009=\u20090.0002), the number of patients who discontinued treatment was not different (14.1% vs. 16.9%, <jats:italic>p<\/jats:italic>\u2009=\u20090.679) for GS compared with GC in the low CCr group. This study suggests that GS should be selected for the treatment of advanced BTC patients with reduced renal function.<\/jats:p>","DOI":"10.1038\/s41598-021-92166-3","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T10:03:33Z","timestamp":1624010613000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparison of gemcitabine-based chemotherapies for advanced biliary tract cancers by renal function: an exploratory analysis of JCOG1113"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4480-0029","authenticated-orcid":false,"given":"Makoto","family":"Ueno","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chigusa","family":"Morizane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuji","family":"Okusaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junki","family":"Mizusawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Kataoka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Ozaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naohiro","family":"Okano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuya","family":"Sugimori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Todaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobumasa","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohisa","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiji","family":"Sano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazutoshi","family":"Tobimatsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akio","family":"Katanuma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Nishina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Shirakawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasushi","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takamasa","family":"Oono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyuki","family":"Kawamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Furukawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohisa","family":"Iwai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Sudo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Miyakawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichirou","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidenori","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoya","family":"Kato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiko","family":"Shioji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshio","family":"Nakagohri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Kamata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Ishii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junji","family":"Furuse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the members of the Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG-HBPOG).","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"92166_CR1","unstructured":"Ministry of Health, Labour and Welfare. Vital statistics Japan. (Ministry of Health, Labour and Welfare, 2020)."},{"key":"92166_CR2","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1158\/2159-8290.CD-17-0245","volume":"7","author":"JW Valle","year":"2017","unstructured":"Valle, J. W., Lamarca, A., Goyal, L., Barriuso, J. & Zhu, A. X. New horizons for precision medicine in biliary tract cancers. Cancer Discov. 7, 943\u2013962 (2017).","journal-title":"Cancer Discov."},{"key":"92166_CR3","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1056\/NEJMoa0908721","volume":"362","author":"J Valle","year":"2010","unstructured":"Valle, J. et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N. Engl. J. Med. 362, 1273\u20131281 (2010).","journal-title":"N. Engl. J. Med."},{"key":"92166_CR4","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1016\/S1470-2045(21)00027-9","volume":"22","author":"A Lamarca","year":"2021","unstructured":"Lamarca, A. et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): A phase 3, open-label, randomised, controlled trial. Lancet. Oncol. 22, 690 (2021).","journal-title":"Lancet. Oncol."},{"key":"92166_CR5","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/S1470-2045(20)30109-1","volume":"21","author":"GK Abou-Alfa","year":"2020","unstructured":"Abou-Alfa, G. K. et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 21, 671\u2013684 (2020).","journal-title":"Lancet Oncol."},{"key":"92166_CR6","first-page":"1","volume":"2020","author":"A Rizzo","year":"2020","unstructured":"Rizzo, A., Ricci, A. D. & Brandi, G. Futibatinib, an investigational agent for the treatment of intrahepatic cholangiocarcinoma: Evidence to date and future perspectives. Expert Opin. Investig. Drugs 2020, 1\u20138 (2020).","journal-title":"Expert Opin. Investig. Drugs"},{"key":"92166_CR7","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/S2468-1253(19)30086-X","volume":"4","author":"M Ueno","year":"2019","unstructured":"Ueno, M. et al. Nivolumab alone or in combination with cisplatin plus gemcitabine in Japanese patients with unresectable or recurrent biliary tract cancer: A non-randomised, multicentre, open-label, phase 1 study. Lancet Gastroenterol. Hepatol. 4, 611 (2019).","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"92166_CR8","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1136\/jitc-2020-SITC2020.0513","volume":"8","author":"C Yoo","year":"2020","unstructured":"Yoo, C. et al. Phase I study of bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with pretreated biliary tract cancer. J. Immunother Cancer 8, 549 (2020).","journal-title":"J. Immunother Cancer"},{"key":"92166_CR9","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1002\/ijc.33013","volume":"147","author":"SA Piha-Paul","year":"2020","unstructured":"Piha-Paul, S. A. et al. Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies. . Int. J. Cancer J. Int. Cancer 147, 2190\u20132198 (2020).","journal-title":"Int. J. Cancer J. Int. Cancer"},{"key":"92166_CR10","doi-asserted-by":"crossref","unstructured":"Rizzo, A. & Brandi, G. First-line chemotherapy in advanced biliary tract cancer ten years after the ABC-02 trial: \u201cAnd yet it moves!\u201d. Cancer Treat Res. Commun. 27, (2021).","DOI":"10.1016\/j.ctarc.2021.100335"},{"key":"92166_CR11","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1016\/S1470-2045(09)70259-1","volume":"10","author":"N Boku","year":"2009","unstructured":"Boku, N. et al. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: A randomised phase 3 study. Lancet Oncol. 10, 1063\u20131069 (2009).","journal-title":"Lancet Oncol."},{"key":"92166_CR12","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1200\/JCO.2012.43.3680","volume":"31","author":"H Ueno","year":"2013","unstructured":"Ueno, H. et al. 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. J. Clin. Oncol. 31, 1640\u20131648 (2013).","journal-title":"J. Clin. Oncol."},{"key":"92166_CR13","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1159\/000362604","volume":"87","author":"S Kobayashi","year":"2014","unstructured":"Kobayashi, S. et al. Renal toxicity associated with weekly cisplatin and gemcitabine combination therapy for treatment of advanced biliary tract cancer. Oncology 87, 30\u201339 (2014).","journal-title":"Oncology"},{"key":"92166_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00280-003-0617-9","volume":"52","author":"GJ Peters","year":"2003","unstructured":"Peters, G. J. et al. Pharmacokinetics of S-1, an oral formulation of ftorafur, oxonic acid and 5-chloro-2,4-dihydroxypyridine (molar ratio 1:0.4:1) in patients with solid tumors. Cancer Chemother. Pharmacol. 52, 1\u201312 (2003).","journal-title":"Cancer Chemother. Pharmacol."},{"key":"92166_CR15","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s10120-004-0306-3","volume":"8","author":"F Nagashima","year":"2005","unstructured":"Nagashima, F., Ohtsu, A., Yoshida, S. & Ito, K. Japanese nationwide post-marketing survey of S-1 in patients with advanced gastric cancer. Gastric Cancer 8, 6\u201311 (2005).","journal-title":"Gastric Cancer"},{"key":"92166_CR16","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/s10120-007-0422-y","volume":"10","author":"T Yamanaka","year":"2007","unstructured":"Yamanaka, T. et al. Analysis of risk factors for severe adverse effects of oral 5-fluorouracil S-1 in patients with advanced gastric cancer. Gastric Cancer 10, 129\u2013134 (2007).","journal-title":"Gastric Cancer"},{"key":"92166_CR17","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s10120-012-0158-1","volume":"16","author":"T Aoyama","year":"2013","unstructured":"Aoyama, T. et al. Risk factors for 6-month continuation of S-1 adjuvant chemotherapy for gastric cancer. Gastric Cancer 16, 133\u2013139. https:\/\/doi.org\/10.1007\/s10120-012-0158-1 (2013).","journal-title":"Gastric Cancer"},{"key":"92166_CR18","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1159\/000180580","volume":"16","author":"DW Cockcroft","year":"1976","unstructured":"Cockcroft, D. W. & Gault, M. H. Prediction of creatinine clearance from serum creatinine. Nephron 16, 31\u201341 (1976).","journal-title":"Nephron"},{"key":"92166_CR19","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1007\/s10147-019-01468-0","volume":"24","author":"K Miyatani","year":"2019","unstructured":"Miyatani, K. et al. Late start and insufficient S-1 dose in adjuvant chemotherapy can lead to poor prognosis in stage II\/III gastric cancer. Int. J. Clin. Oncol. 24, 1190\u20131196 (2019).","journal-title":"Int. J. Clin. Oncol."},{"key":"92166_CR20","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1038\/sj.bjc.6602804","volume":"93","author":"M Tsukuda","year":"2005","unstructured":"Tsukuda, M. et al. Randomized scheduling feasibility study of S-1 for adjuvant chemotherapy in advanced head and neck cancer. Br. J. Cancer 93, 884\u2013889 (2005).","journal-title":"Br. J. Cancer"},{"key":"92166_CR21","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1007\/s10120-015-0536-6","volume":"19","author":"E Booka","year":"2016","unstructured":"Booka, E. et al. Development of an S-1 dosage formula based on renal function by a prospective pharmacokinetic study. Gastric Cancer 19, 876\u2013886 (2016).","journal-title":"Gastric Cancer"},{"key":"92166_CR22","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1093\/jjco\/hyr090","volume":"41","author":"H Ueno","year":"2011","unstructured":"Ueno, H. et al. Multicenter phase II study of gemcitabine and S-1 combination therapy (GS Therapy) in patients with metastatic pancreatic cancer. Jpn. J. Clin. Oncol. 41, 953\u2013958 (2011).","journal-title":"Jpn. J. Clin. Oncol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-92166-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-92166-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-92166-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T10:27:36Z","timestamp":1670063256000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-92166-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,18]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["92166"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-92166-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2021,6,18]]},"assertion":[{"value":"18 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr. Ueno reports grants and personal fees from Yakult Honsha, grants and personal fees from Taiho Pharmaceutical, AstraZeneca, Merck Serono, MSD, Daiichi Sankyo and Ono Pharmaceutical, personal fees from Nihon Servier, grants from Astellas Pharma, Eisai, Sumitomo Dainippon Pharma and Incyte. Dr. Morizane reports grants and personal fees from Yakult Honsha, J-Pharma, AstraZeneca, MSD and Taiho Pharmaceutical, grants from Eisai, Merck Biopharma and Ono Pharmaceutical, personal fees from Teijin Pharma, Novartis and Abbvie. Dr. Okusaka reports grants and personal fees from Eli Lilly, Taiho Pharmaceutical, Pfizer Japan and Yakult Honsha, personal fees from Meiji Seika Pharma, grants and personal fees from Ono Pharmaceutical, Eisai, Sumitomo Dainippon Pharma, Bristol-Myers Squibb, Bayer Yakuhin, Chugai Pharmaceutical, Zeria Pharmaceutical, Daiichi Sankyo and MSD, grants from Kyowa Hakko Kirin, NanoCarrier and Baxter, personal fees from EA Pharma, FUJIFILM RI Pharma, Celgene, Teijin Pharma, Shire, AbbVie, Takeda Pharmaceutical, Mundipharma, Nihon Servier and Nippon Shinyaku. Mr. Mizusawa reports grants from the Ministry of Health, Labour and Welfare, Japan and Japan Agency for Medical Research and Development (AMED), personal fees from Chugai Pharmaceutical. Dr. Ikeda reports grants from Yakult Honsha, Ono Pharmaceutical, AstraZeneca, J-Pharma, Merck Serono, Bristol-Myers Squibb, Pfizer, Takeda Pharmaceutical and Chiome Bioscience, personal fees and grants from ASLAN, Nihon Servier, NanoCarrier, Novartis, Bayer Yakuhin, Eli Lilly, MSD and Chugai Pharmaceutical, personal fees from Taiho Phamaceutical, Sumitomo Dainippon Pharma, Teijin Pharma, Mylan, Astellas Pharma, EA Pharma, Shire, Gilead and Otsuka. Dr. Okano reports personal fees from Taiho Pharmaceutical, Eli Lilly Japan, Kyowa Hakko Kirin, Eisai, Bayer Yakuhin, Chugai Pharmaceutical, J-Pharma, Ono Pharmaceutical, Takeda Pharmaceutical and Merck BioPharma. Dr. Shimizu reports grants from Sumitomo Dainippon Pharma, Yakult Honsha, Incyte and AstraZeneca. Dr. Mizuno reports grants and personal fees from Taiho Pharmaceutical, grants from the Ministry of Health, Labour and Welfare, Japan, grants and personal fees from Novartis, AstraZeneca, MSD and Yakult Honsha, grants from NanoCarrier, Eisai, Sumitomo Dainippon Pharma, ASLAN Pharmaceuticals, Incyte and Ono Pharmaceutical, personal fees from Teijin Pharma. Dr. Takahashi reports grants from Taiho Pharmaceutical. Dr. Ishii reports personal fees from Ono Pharmaceutical, Yakult Honsha, Taiho Pharmaceutical, Eli Lilly Japan and Teijin Pharma. Dr. Furuse reports grants from the National Cancer Center Research and Development Fund and a Grant-in-Aid for Clinical Cancer Research from the Ministry of Health, Labour and Welfare of Japan, personal fees from Eisai, Bayer Yakuhin, Taiho Pharmaceutical, Ono Pharmaceutical, Novartis, Yakult Honsha, Teijin pharma, Shionogi, EA Pharma, Eli Lilly Japan, Takeda Pharmaceutical, Chugai Pharmaceutical, Mochida Pharmaceutical, Nihon Servier, Sanofi, Fujifilm Toyama Chemical, Nobelpharma, Pfizer, Sawai Pharmaceutical, Daiichi Sankyo, Sumitomo Dainippon Pharma, Merck Serono, Nippon Kayaku, MSD, Shire and Kyowa Hakko Kirin, grants from Ono Pharmaceutical, MSD, Sumitomo Dainippon Pharma, J-Pharma, Yakult Honsha, AstraZeneca, Daiichi Sankyo, Eisai, Bayer Yakuhin, Pfizer, NanoCarrier, Kyowa Hakko Kirin, Taiho Pharmaceutical, Chugai Pharmaceutical, Sanofi, Takeda Pharmaceutical, Mochida Pharmaceutical, Astellas Pharma and Eli Lilly Japan. All other authors declare no conflicts of interest in relation to the present work.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12885"}}