{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:02:22Z","timestamp":1790596942422,"version":"4.1.0"},"reference-count":14,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,30]],"date-time":"2019-01-30T00:00:00Z","timestamp":1548806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p>This phase I study aimed to determine tolerability and preliminary efficacy of single\u2010agent alpelisib (BYL719) in Japanese patients with advanced solid malignancies. The primary objective of the study was to estimate the maximum tolerated dose (MTD) and\/or recommended phase II dose (RP2D) of oral alpelisib in patients with advanced solid tumors who had progressed despite standard therapy. The expansion part included patients with <jats:italic>PIK3CA<\/jats:italic> mutation\/amplification; safety, preliminary efficacy, pharmacokinetic (PK)\/pharmacodynamic profile, and food effect on the PK profile of alpelisib at the MTD\/RP2D were determined. Oral alpelisib was given as a single agent on a continuous 28\u2010day treatment cycle once daily. Overall, 33 patients received alpelisib. Dose\u2010limiting toxicities were observed in 2 patients in the escalation part (at 400\u00a0mg\/day) and 1 patient in the expansion part (at 350\u00a0mg\/day). The RP2D of alpelisib was determined as 350\u00a0mg\/day based on overall safety profile in the dose escalation part and previous data from a Western population; the MTD was not determined. The most common all\u2010grade treatment\u2010suspected adverse events were hyperglycemia and maculopapular rash (48.5% each) and diarrhea (45.5%). The PK of alpelisib in the Japanese population was similar to that reported in the Western population. The overall response rate, disease control rate, and median progression\u2010free survival at 350\u00a0mg\/day were 3%, 57.6%, and 3.4\u00a0months, respectively. Alpelisib as single agent showed a favorable safety profile and encouraging preliminary efficacy in Japanese patients with advanced solid tumors.<\/jats:p>","DOI":"10.1111\/cas.13923","type":"journal-article","created":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T05:39:10Z","timestamp":1545889150000},"page":"1021-1031","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Phase I study of alpelisib (BYL719), an \u03b1\u2010specific PI3K inhibitor, in Japanese patients with advanced solid tumors"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6849-2297","authenticated-orcid":false,"given":"Yuichi","family":"Ando","sequence":"first","affiliation":[{"name":"Nagoya University Hospital  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Iwasa","sequence":"additional","affiliation":[{"name":"National Cancer Center Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunji","family":"Takahashi","sequence":"additional","affiliation":[{"name":"The Cancer Institute Hospital of Japanese Foundation for Cancer Research  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Saka","sequence":"additional","affiliation":[{"name":"Nagoya Medical Center  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Kakizume","sequence":"additional","affiliation":[{"name":"Novartis Pharma K.K.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuto","family":"Natsume","sequence":"additional","affiliation":[{"name":"Novartis Pharma K.K.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Suenaga","sequence":"additional","affiliation":[{"name":"Novartis Pharma K.K.  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SABCS 2017: American Association for Cancer Research 2017."},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-1080"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcas.13923","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.13923","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T21:42:22Z","timestamp":1694468542000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.13923"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,30]]},"references-count":14,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1111\/cas.13923"],"URL":"https:\/\/doi.org\/10.1111\/cas.13923","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,30]]},"assertion":[{"value":"2018-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}