{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T15:20:53Z","timestamp":1759159253252},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T00:00:00Z","timestamp":1429228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2015,7]]},"abstract":"Abstract<\/jats:title>We investigated the efficacy and safety of vemurafenib in Japanese patients with unresectable or recurrent melanoma with BRAF<\/jats:italic>V<\/jats:italic><\/jats:sup><\/jats:styled-content>600<\/jats:italic><\/jats:sup> mutations. This was a two\u2010step open\u2010label multicenter phase I\/II<\/jats:styled-content> study. Step 1 evaluated the initial safety of vemurafenib 960\u00a0mg administrated p.o. twice daily in three patients. In step 2, eight patients received vemurafenib 960\u00a0mg administrated p.o. twice daily for 28\u2010day treatment cycles; the primary outcome measure was response rate, as determined by independent review committee using R<\/jats:styled-content>esponse E<\/jats:styled-content>valuation C<\/jats:styled-content>riteria in S<\/jats:styled-content>olid T<\/jats:styled-content>umors version 1.1. Adverse events (AE<\/jats:styled-content>) experienced by five or more patients were arthralgia (n<\/jats:italic>\u00a0=\u00a010), myalgia (n<\/jats:italic>\u00a0=\u00a08), alopecia (n<\/jats:italic>\u00a0=\u00a07), and rash, maculopapular rash and decreased appetite (n<\/jats:italic>\u00a0=\u00a05 each). Three patients had grade 3 AE<\/jats:styled-content>. One serious AE<\/jats:styled-content> occurred in one patient (abnormal hepatic function). Six patients required dose reduction because of AE<\/jats:styled-content>. One patient died within 28\u00a0days after the last dose, but death was caused by disease progression and not associated with the study drug. In the eight patients in step 2, overall response rate was 75.0%, none had a complete response and six had a partial response (75.0%). Median response duration was 240.0\u00a0days, disease control rate 87.5%, median progression\u2010free survival 416.0\u00a0days and median overall survival 443.0\u00a0days. In conclusion, vemurafenib treatment resulted in an overall response rate of 75% in Japanese patients with metastatic melanoma with BRAF<\/jats:italic>V<\/jats:italic><\/jats:sup><\/jats:styled-content>600<\/jats:italic><\/jats:sup> mutations. All toxicities were manageable.<\/jats:p>","DOI":"10.1111\/1346-8138.12873","type":"journal-article","created":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T10:58:45Z","timestamp":1429268325000},"page":"661-666","source":"Crossref","is-referenced-by-count":16,"title":["Phase I\/II<\/scp> study of vemurafenib in patients with unresectable or recurrent melanoma with BRAF<\/i>V<\/i><\/sup><\/scp>600<\/i><\/sup> mutations"],"prefix":"10.1111","volume":"42","author":[{"given":"Naoya","family":"Yamazaki","sequence":"first","affiliation":[{"name":"Department of Dermatologic Oncology National Cancer Center Hospital Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshio","family":"Kiyohara","sequence":"additional","affiliation":[{"name":"Department of Dermatology Shizuoka Cancer Center Shizuoka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naofumi","family":"Sugaya","sequence":"additional","affiliation":[{"name":"Chugai Pharmaceutical Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Uhara","sequence":"additional","affiliation":[{"name":"Department of Dermatology Shinshu University School of Medicine Nagano Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,4,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra052166"},{"key":"e_1_2_7_3_1","first-page":"3","article-title":"Recent advances in melanoma research","volume":"55","author":"Takata M","year":"2007","journal-title":"Shinshu Med J"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-009-0941-0"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09454"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-8-39"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711741105"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043369"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2007.12.003"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000091"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2012.03.005"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103782"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70012-9"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2011-0505-OA"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-013-2324-5"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2012.11155.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1210093"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2010.04822.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2008.10.043"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08902"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08833"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.12.040"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","unstructured":"SigrunH OmidH ThuyASet\u00a0al.Phase 2 study of vemurafenib in patients with locally advanced unresectable stage IIIC or metastatic melanoma and activating exon 15 BRAF mutations other than V600E. 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