{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T18:06:53Z","timestamp":1770487613713,"version":"3.49.0"},"reference-count":27,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2015,10,23]],"date-time":"2015-10-23T00:00:00Z","timestamp":1445558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2015,10,23]],"date-time":"2015-10-23T00:00:00Z","timestamp":1445558400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncology"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Purpose:&lt;\/i&gt;&lt;\/b&gt; This phase I study (EudraCT No. 2006-001177-25) investigated aflibercept, a vascular endothelial growth factor decoy receptor protein (VEGF Trap), in combination with docetaxel, cisplatin, and 5-fluorouracil in patients with advanced solid tumors. &lt;b&gt;&lt;i&gt;Patients and Methods:&lt;\/i&gt;&lt;\/b&gt; Patients received 2, 4, or 6 mg\/kg of intravenous aflibercept with docetaxel 75 mg\/m&lt;sup&gt;2&lt;\/sup&gt;, cisplatin 75 mg\/m&lt;sup&gt;2&lt;\/sup&gt;, and 5-fluorouracil 750 mg\/m&lt;sup&gt;2&lt;\/sup&gt; in 3-week cycles until disease progression or unacceptable toxicity. Primary objectives were to evaluate dose-limiting toxicities (DLTs) during cycle 1 and to determine the recommended phase II dose. Pharmacokinetics, tolerability, and antitumor activity were also investigated. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Forty-four patients were enrolled and treated (29 patients in a dose-escalation phase and 15 patients in an expansion cohort). Following three cases of febrile neutropenia in patients receiving aflibercept at 4 mg\/kg, the protocol was amended to allow earlier granulocyte colony-stimulating factor support (from day 6) and prophylactic use of ciprofloxacin. Subsequently, there were two DLTs: febrile neutropenia (2 mg\/kg) and grade 4 pulmonary embolism (6 mg\/kg). An excess of free over VEGF-bound aflibercept was observed at 6 mg\/kg. The most frequent grade 3\/4 adverse events (AEs) were neutropenia (54.5%), lymphopenia (47.7%), and stomatitis (38.6%). AEs associated with VEGF blockade (any grade) included epistaxis (61.4%), dysphonia (40.9%), hypertension (38.6%), and proteinuria (11.4%). There were 15 partial responses, including 9 in patients with gastroesophageal cancers. Thirteen patients had stable disease. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; Aflibercept 6 mg\/kg administered every 3 weeks in combination with docetaxel, cisplatin, and 5- fluorouracil is the recommended dose for further clinical development based on tolerability, pharmacokinetics, and antitumor activity.<\/jats:p>","DOI":"10.1159\/000440958","type":"journal-article","created":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T21:04:46Z","timestamp":1445547886000},"page":"10-20","source":"Crossref","is-referenced-by-count":3,"title":["Phase I Dose-Escalation and Pharmacokinetic Study of Intravenous Aflibercept in Combination with Docetaxel, Cisplatin, and 5-Fluorouracil in Patients with Advanced Solid Malignancies"],"prefix":"10.1159","volume":"90","author":[{"given":"Rastislav","family":"Bahleda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jackie","family":"Baker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Massard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sirish M.","family":"Gadgeel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7275-7008","authenticated-orcid":false,"given":"Jane 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