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This study sought to determine the recommended dose of aflibercept, a recombinant fusion protein targeting VEGF-A, VEGF-B and placental growth factor (PlGF), combined with docetaxel in Japanese patients with advanced solid malignancies.\u00a0This phase I study was planned to include 12 patients following a 3\u2009+\u20093 algorithm to determine the maximum tolerated dose of aflibercept combined with docetaxel in patients with metastatic or unresectable solid tumors (trial registration: NCT00545246). Docetaxel (75\u00a0mg\/m<jats:sup>2<\/jats:sup> every 3\u00a0weeks or 60\u00a0mg\/m<jats:sup>2<\/jats:sup> after protocol amendment) was combined with escalating doses of aflibercept (2, 4 and 6\u00a0mg\/kg every 4\u00a0weeks). Free and VEGF-bound aflibercept were measured to assess free aflibercept in excess of the VEGF-bound form.\u00a0At the starting dose of the combination, 3 of 6 patients treated experienced febrile neutropenia. After reducing the docetaxel dose to 60\u00a0mg\/m<jats:sup>2<\/jats:sup> in step 2 and permitting therapeutic granulocyte colony-stimulating factor (G-CSF) use, 2 of 3 patients in both cohorts experienced febrile neutropenia. Five patients (42%) had a partial response and 4 patients had stable disease (33%). Free aflibercept in excess of the VEGF-bound form was not maintained at this dose level.\u00a0The dose limiting toxicity (DLT) of aflibercept combined with docetaxel was febrile neutropenia, which occurred in 2 of 3 Japanese patients at the lowest aflibercept dose level (2\u00a0mg\/kg) combined with docetaxel (60\u00a0mg\/m<jats:sup>2<\/jats:sup>) and therapeutic G-CSF use. A recommended dose for further studies was not determined because of the DLT at the starting dose.\n<\/jats:p>","DOI":"10.1007\/s10637-022-01267-x","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T13:13:51Z","timestamp":1656594831000},"page":"1032-1041","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phase I study of aflibercept in combination with docetaxel in Japanese patients with advanced solid malignancies"],"prefix":"10.1007","volume":"40","author":[{"given":"Yu","family":"Sunakawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keishiro","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"1267_CR1","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1038\/nbt0697-510","volume":"15","author":"J Folkman","year":"1997","unstructured":"Folkman J (1997) Addressing tumor blood vessels. 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Yu Sunakawa reports research grants (in the past 36\u00a0months) from Chugai Pharma, Taiho Pharma, Takeda, and Otsuka Pharma; and honoraria\/lecture fees\/speakers\u2019 fees (in the past 36\u00a0months) from Eli Lilly Japan, Bristol-Myers Squibb, Chugai Pharma, Ono Pharma, Daiichi-Sankyo, Sysmex, Taiho Pharma, Merck Biopharma, Takeda, Bayer, and Guardant Japan. Keishiro Takahashi and Osamu Kawaguchi are employees of Sanofi and may hold shares and\/or stock options in the company. Nobuyuki Yamamoto reports honoraria\/lecture fees\/speakers\u2019 fees (in the past 36 months) from MSD, Chugai Pharma, Ono Pharma, AstraZeneca, Takeda Pharma, Eli Lilly Japan, Novartis, Pfizer, Janssen, Taiho Pharma, Daiichi-Sankyo, Amgen, Eisai, Toppan Printing, and Boehringer Ingelheim.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}