{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:53:16Z","timestamp":1787964796271,"version":"build-2784847793"},"reference-count":17,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,10,5]],"date-time":"2016-10-05T00:00:00Z","timestamp":1475625600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In the adjuvant setting for malignant melanoma, interferon (<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>)\u2010\u03b1\u20102b and pegylated (<jats:styled-content style=\"fixed-case\">PEG<\/jats:styled-content>) <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u2010\u03b1\u20102b were approved in several countries including the USA before these were approved in Japan. To resolve the \u201cdrug\u2010lag\u201d issue, this phase I study was designed to evaluate the safety and tolerability in Japanese patients with stage <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> malignant melanoma who had undergone surgery, by treating with <jats:styled-content style=\"fixed-case\">PEG IFN<\/jats:styled-content>\u2010\u03b1\u20102b. As with a previously reported phase <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> study, patients were to receive <jats:styled-content style=\"fixed-case\">PEG IFN<\/jats:styled-content>\u2010\u03b1\u20102b 6 \u03bcg\/kg per week s.c. during an 8\u2010week induction phase, followed by a maintenance phase at a dose of 3 \u03bcg\/kg per week up to 5 years. Dose\u2010limiting toxicity and pharmacokinetics were assessed during the initial 8 weeks. Of the nine patients enrolled, two patients had dose\u2010limiting toxicities that resolved after discontinuation of treatment. The most frequently reported drug\u2010related adverse events (<jats:styled-content style=\"fixed-case\">DRAE<\/jats:styled-content>) included pyrexia, decreased neutrophil and white blood cell counts, and arthralgia. Grade 3 <jats:styled-content style=\"fixed-case\">DRAE<\/jats:styled-content> included decreased neutrophil count. No deaths, serious adverse events and grade 4 adverse events were reported. Distant metastasis occurred in one patient. No apparent differences in area under the concentration\u2013time curve and maximum observed serum concentration were observed between Japanese and historical non\u2010Japanese pharmacokinetic data, suggesting no marked racial differences. No neutralizing antibody was detected in these patient samples. <jats:styled-content style=\"fixed-case\">PEG IFN<\/jats:styled-content>\u2010\u03b1\u20102b was tolerated in Japanese patients, and eventually approved in Japan in May 2015 for adjuvant therapy in patients with stage <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content> malignant melanoma. Because the number of patients was limited, further investigation would be crucial.<\/jats:p>","DOI":"10.1111\/1346-8138.13338","type":"journal-article","created":{"date-parts":[[2016,4,18]],"date-time":"2016-04-18T05:12:45Z","timestamp":1460956365000},"page":"1146-1153","source":"Crossref","is-referenced-by-count":11,"title":["Phase I study of pegylated interferon\u2010alpha\u20102b as an adjuvant therapy in Japanese patients with malignant melanoma"],"prefix":"10.1111","volume":"43","author":[{"given":"Naoya","family":"Yamazaki","sequence":"first","affiliation":[{"name":"Department of Dermatologic Oncology National Cancer Center Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Uhara","sequence":"additional","affiliation":[{"name":"Department of Dermatology Shinshu University School of Medicine Matsumoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidefumi","family":"Wada","sequence":"additional","affiliation":[{"name":"Environmental Immuno\u2010Dermatology Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Japan Development MSD K.K. 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