Supplementary Material for: Phase I Dose-Escalation and Pharmacokinetic Study of Intravenous Aflibercept in Combination with Docetaxel, Cisplatin, and 5-Fluorouracil in Patients with Advanced Solid Malignancies Bahleda R. Baker J. Massard C. Gadgeel S.M. Rogers J.E. Izzedine H. Deutsch E. Garris J.L. Khan A. Boelle E. 10.6084/m9.figshare.5128819.v1 https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Phase_I_Dose-Escalation_and_Pharmacokinetic_Study_of_Intravenous_Aflibercept_in_Combination_with_Docetaxel_Cisplatin_and_5-Fluorouracil_in_Patients_with_Advanced_Solid_Malignancies/5128819 <b><i>Purpose:</i></b> 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. <b><i>Patients and Methods:</i></b> Patients received 2, 4, or 6 mg/kg of intravenous aflibercept with docetaxel 75 mg/m<sup>2</sup>, cisplatin 75 mg/m<sup>2</sup>, and 5-fluorouracil 750 mg/m<sup>2</sup> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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. 2015-10-23 00:00:00 VEGF Trap DCF chemotherapy Aflibercept Solid tumors