{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:24:26Z","timestamp":1793823866293,"version":"4.6.1"},"reference-count":6,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T00:00:00Z","timestamp":1670198400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T00:00:00Z","timestamp":1670198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Invest New Drugs"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Ocular toxicities arising from anti-cancer drugs occur sporadically and are sometimes underestimated because they are not life-threatening. Reports focusing on ocular toxicities from cancer therapy are limited. We investigated the detailed progress of ocular toxicities of anti-cancer drugs including first-in-class ones.\u00a0A retrospective review of medical records was conducted for patients who were involved in early phase clinical trials with scheduled ophthalmologic examinations according to their protocols between January 2014 and August 2021. Patients with ocular toxicity suspected to be related to the investigational drugs in the ophthalmic examination were investigated in detail.\u00a0In total, 37 ocular toxicities related to investigational drugs occurred in 7.6% of patients (33\/434). The median age of the 33 patients was 61\u00a0years (range, 33\u201376\u00a0years), and 20 were male. Causal drugs with a high incidence of ocular toxicities were HSP90 inhibitors and FGFR inhibitors. Retinopathy was most frequent, while conjunctivitis, dry eye, keratitis, keratopathy, and uveitis were also observed. Dim vision as a subjective finding was a unique adverse event. Most patients developed ocular toxicities even though their dose was below the drug\u2019s maximum tolerated dose. Except for one case, all ocular toxicities occurred bilaterally. About 60% (22\/37) of ocular toxicity cases needed a temporary hold of the drug. All except for three cases fully recovered.\u00a0This study reported the risks and timing of the onset of a variety of ocular toxicities of anti-cancer drugs, which were fundamentally controllable. (Trial registration number.\u00a0Retrospectively registered)<\/jats:p>","DOI":"10.1007\/s10637-022-01321-8","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T17:05:51Z","timestamp":1670259951000},"page":"173-181","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Ocular toxicity of investigational anti-cancer drugs in early phase clinical trials"],"prefix":"10.1007","volume":"41","author":[{"given":"Shigemasa","family":"Takamizawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Katsuya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ning","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaaki","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Koyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Sudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Iwasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Yonemori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigenobu","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,5]]},"reference":[{"key":"1321_CR1","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1007\/s40265-021-01507-z","volume":"81","author":"BH Fortes","year":"2021","unstructured":"Fortes BH, Tailor PD, Dalvin LA (2021) Ocular toxicity of targeted anticancer agents. Drugs 81:771\u2013823","journal-title":"Drugs"},{"key":"1321_CR2","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1158\/1078-0432.CCR-19-2035","volume":"26","author":"F Facchinetti","year":"2020","unstructured":"Facchinetti F, Hollebecque A, Bahleda R et al (2020) Facts and new hopes on selective FGFR inhibitors in solid tumors. Clin Cancer Res 26:764\u2013774","journal-title":"Clin Cancer Res"},{"key":"1321_CR3","unstructured":"U.S. Department of Health and Human Services (2017) Common terminology criteria for adverse events (CTCAE) Version 5.0.\u00a0https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/docs\/ctcae_v5_quick_reference_5x7.pdf. Accessed 2 Dec 2022"},{"key":"1321_CR4","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1007\/s10637-019-00780-w","volume":"38","author":"N Yamamoto","year":"2020","unstructured":"Yamamoto N, Ryoo BY, Keam B et al (2020) A phase 1 study of oral ASP5878, a selective small-molecule inhibitor of fibroblast growth factor receptors 1\u20134, as a single dose and multiple doses in patients with solid malignancies. Invest New Drugs 38:445\u2013456","journal-title":"Invest New Drugs"},{"key":"1321_CR5","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1111\/cas.14265","volume":"111","author":"T Koyama","year":"2020","unstructured":"Koyama T, Shimizu T, Iwasa S et al (2020) First-in-human phase I study of E7090, a novel selective fibroblast growth factor receptor inhibitor, in patients with advanced solid tumors. Cancer Sci 111:571\u2013579","journal-title":"Cancer Sci"},{"key":"1321_CR6","doi-asserted-by":"publisher","first-page":"4888","DOI":"10.1158\/1078-0432.CCR-18-3334","volume":"25","author":"R Bahleda","year":"2019","unstructured":"Bahleda R, Italiano A, Hierro C et al (2019) Multicenter phase I study of erdafitinib (JNJ-42756493), oral pan-fibroblast growth factor receptor inhibitor, in patients with advanced or refractory solid tumors. Clin Cancer Res 25:4888\u20134897","journal-title":"Clin Cancer Res"}],"container-title":["Investigational New Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-022-01321-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10637-022-01321-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10637-022-01321-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T13:08:34Z","timestamp":1679404114000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10637-022-01321-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,5]]},"references-count":6,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["1321"],"URL":"https:\/\/doi.org\/10.1007\/s10637-022-01321-8","relation":{},"ISSN":["0167-6997","1573-0646"],"issn-type":[{"value":"0167-6997","type":"print"},{"value":"1573-0646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,5]]},"assertion":[{"value":"31 May 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 December 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Institutional Review Board of NCCH (NCCH 2014\u2013148). The study was conducted according to the principles of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The informed consent was waived in accordance with the local regulation.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publish"}},{"value":"ST has nothing to disclose. YK has nothing to disclose. YC has nothing to disclose. TM has nothing to disclose. TK has received grants from PACT Pharma, and personal fees from Chugai, and Sysmex. KS has received personal fees from Pfizer, Eisai, and AstraZeneca. TY has received grants from AMGEN, AstraZeneca, Takeda, Daiichi Sankyo, ONO Pharmaceutical Co., Ltd, MSD, Abbvie, Novartis, Chugai, Merck, Blueprint, and BMS, and personal fees from AstraZeneca, Takeda, Boehringer-Ingelheim, TAIHO, Chugai, Novartis, Lilly, MSD, ONO Pharmaceutical Co., Ltd, Roche, ArcherDX, Invitae, and BMS. SK has received grants from Chugai, Takeda, ASLAN, AstraZeneca, Eisai, Pfizer,\u00a0Boehringer Ingelheim, Incyte, Lilly,\u00a0Bristol Myers Squibb, MSD, and Astellas, and personal fees from Chugai, Takeda, Termo, Incyte, and Eisai. SI has received personal fees from Daiichi-Sankyo, Lilly, ONO Pharmaceutical Co., Ltd, Chugai, and Taiho. KY has received personal fees from Pfizer, Eisai, AstraZeneca, Lilly, Takeda, Chugai, Fuji Film Pharma, Novartis, and Genmab. TS has received grants from Novartis, Lilly, Daiichi-Sankyo, Abbvie, Bristol-Myers Squibb, Eisai, AstraZeneca, Pfizer, Loxo Oncology, Takeda, Incyte, Chordia Therapeutics, 3D-Medicine, Symbio Pharmaceuticals, PharmaMar, Five Prime, and Astellas, and personal fees from Lilly, MSD, Chugai, Abbvie, Daiichi-Sankyo, Takeda, and Chordia Therapeutics. NY has received grants from Chugai, Taiho, Eisai, Lilly, Quintiles, Astellas, BMS, Novartis, Daiichi-Sankyo, Pfizer, Boehringer Ingelheim, Kyowa-Hakko Kirin, Bayer, ONO Pharmaceutical Co., Ltd, Takeda, Janssen Pharma, MSD, Merck, GSK, Sumitomo Dainippon, Chiome Bioscience Inc., Otsuka, Carna Biosciences, Genmab, and Shionogi, and personal fees from ONO Pharmaceutical Co., Ltd, Chugai, AstraZeneca, Pfizer, Lilly, BMS, Eisai, Otsuka, Takeda, Boehringer Ingelheim, Cimic, and Sysmex. SS has received personal fees from ONO Pharmaceutical Co., Ltd.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}