Phase i dose-escalation study of aflibercept in combination with docetaxel and cisplatin in patients with advanced solid tumours

Abstract

Background: This phase I cohort study investigated aflibercept (vascular endothelial growth factor (VEGF) trap) plus docetaxel and cisplatin in patients with advanced solid tumours.Methods:Patients received intravenous aflibercept 4, 5, or 6 mg kg-1 with docetaxel and cisplatin (75 mg m-2 each) on day 1 of a 3-week cycle until progressive disease or unacceptable toxicity. Primary objectives were determining cycle 1 dose-limiting toxicities (DLTs) and the aflibercept recommended phase II trial dose (RP2D) for this combination.Results:During the dose-escalation phase (n16), there were two DLTs of febrile neutropenia (at 4 and 5 mg kg-1). Granulocyte colony-stimulating factor prophylaxis was subsequently recommended. The RP2D of aflibercept was established at 6 mg kg-1 and administered to 14 additional patients. The most frequent grade 3/4 adverse events (AEs) were neutropenia (43.3%), stomatitis (20.0%), asthenia/fatigue (20.0%), and hypertension (16.7%). All-grade AEs associated with VEGF blockade included epistaxis (83.3%), dysphonia (70.0%), proteinuria (53.3%), and hypertension (50.0%). There were five partial responses (16.7%) and 18 cases of stable disease (60.0%) (lasting 3 months in 10 patients). There were no pharmacokinetic (PK) interactions between the three drugs.Conclusion:Aflibercept 6 mg kg -1 with docetaxel and cisplatin 75 mg m-2 every 3 weeks is the RP2D based on tolerability, antitumour activity, and PKs. © 2012 Cancer Research UK All rights reserved.