{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T09:56:07Z","timestamp":1697536567441},"reference-count":9,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,6,18]],"date-time":"2012-06-18T00:00:00Z","timestamp":1339977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:p>Preclinical models have shown that <jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content>\u2010101 (4\u2010[3,5\u2010bis(trimethylsilyl) benzamide] benzoic acid), an oral synthetic retinoid, has antitumor activity in hepatocellular carcinoma (<jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content>). We conducted a phase I study in Japanese patients with advanced <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> to examine the pharmacokinetics, recommended dose, safety, and efficacy of <jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content>\u2010101. The administered dose of <jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content>\u2010101 was 10\u00a0mg\/day in four patients (level 1), 20\u00a0mg\/day in six (level 2), and 30\u00a0mg\/day in three (level 3). There was no dose\u2010limiting toxicity at level 1. Only one patient each had dose\u2010limiting toxicity at level 2 (grade 2 fatigue, recovery requiring eight or more consecutive days of rest) and at level 3 (grade 3 splenic vein thrombosis). Level 3 (30\u00a0mg\/day) was considered the maximum tolerated dose and 20\u00a0mg\/day the recommended dose by a panel of medical experts, placing maximum emphasis on safety. The most frequent adverse events were fatigue, headache, and dermal symptoms such as rash. Pharmacokinetic parameters in Japanese patients with <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> were similar to those in patients in the United States, most of whom were Caucasian. Although no patient had a complete or partial response, the disease control rate was 38.5%. In conclusion, the recommended dose of <jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content>\u2010101 for patients with <jats:styled-content style=\"fixed-case\">HCC<\/jats:styled-content> is 20\u00a0mg\/day. <jats:styled-content style=\"fixed-case\">TAC<\/jats:styled-content>\u2010101 had an acceptable toxicity profile, warranting further evaluation in clinical trials. (<jats:italic>Cancer Sci<\/jats:italic>, doi: 10.1111\/j.1349\u20107006.2012.02334.x, 2012)<\/jats:p>","DOI":"10.1111\/j.1349-7006.2012.02334.x","type":"journal-article","created":{"date-parts":[[2012,5,16]],"date-time":"2012-05-16T07:09:13Z","timestamp":1337152153000},"page":"1524-1530","source":"Crossref","is-referenced-by-count":6,"title":["Phase I study of <scp>TAC<\/scp>\u2010101, an oral synthetic retinoid, in Japanese patients with advanced hepatocellular carcinoma"],"prefix":"10.1111","volume":"103","author":[{"given":"Takuji","family":"Okusaka","sequence":"first","affiliation":[{"name":"Hepatobiliary and Pancreatic Oncology Division National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Ueno","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Pancreatic Oncology Division National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Division of Hepatobiliary and Pancreatic Oncology National Cancer Center Hospital East Kashiwa Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoriko","family":"Takezako","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Pancreatic Oncology Division National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chigusa","family":"Morizane","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Pancreatic Oncology Division National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,6,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.196"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0708857"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(08)70285-7"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006561329512"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006567229929"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.3727\/0965040041791464","article-title":"4\u2010[3,5\u2010Bis(trimethylsilyl)benzamido] benzoic acid inhibits angiogenesis in colon cancer through reduced expression of vascular endothelial growth factor","volume":"14","author":"Minagawa N","year":"2004","journal-title":"Oncol Res"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2002.02.090"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-008-0406-2"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.3.205"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1349-7006.2012.02334.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1349-7006.2012.02334.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T07:17:51Z","timestamp":1697440671000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1349-7006.2012.02334.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,6,18]]},"references-count":9,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2012,8]]}},"alternative-id":["10.1111\/j.1349-7006.2012.02334.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1349-7006.2012.02334.x","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6,18]]}}}