Title: Intravenous aflibercept administered in combination with irinotecan, 5-fluorouracil and leucovorin in patients with advanced solid tumours: Results from the expansion cohort of a phase I study
Authors: Khayat, David ×
Tejpar, Sabine
Spano, Jean-Philippe
Verslype, Chris
Bloch, Joël
Vandecaveye, Vincent
Assadourian, Sylvie
Soussan-Lazard, Karen
Cartot-Coton, Sylvaine
Van Cutsem, Eric #
Issue Date: Mar-2013
Publisher: Pergamon
Series Title: European Journal of Cancer vol:49 issue:4 pages:790-797
Article number: S0959-8049(12)00834-9
Abstract: BACKGROUND: Following the dose-escalation stage, this double-blind expansion stage of the phase I study evaluated the safety, pharmacodynamics, pharmacokinetics, anti-vascular effects and antitumour activity of aflibercept 4mg/kg with irinotecan, 5-fluorouracil and leucovorin (LV5FU2). PATIENTS AND METHODS: Patients with advanced solid tumours were randomised at cycle-1 to placebo or aflibercept (4mg/kg) on day 1 then irinotecan-LV5FU2 on days 1 and 2. Subsequently, all patients received aflibercept with irinotecan-LV5FU2 every 2weeks. Anti-vascular effects were assessed using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). RESULTS: Twenty-seven patients were treated; 14 received placebo in cycle-1 followed by aflibercept in later cycles and 13 received aflibercept 4mg/kg upfront. The median number of aflibercept cycles was 16 (range 1-44), 12 patients received ⩾20 cycles. Most frequent grade 3/4 adverse events were neutropenia (37%), fatigue (33%) and hypertension (30%). No anti-aflibercept antibodies were detected. Four patients achieved partial responses and 17 had stable disease, lasting >3months in 14 patients. Plasma levels of free over vascular endothelial growth factor-bound aflibercept were adequate, with steady-state achieved from cycle-3. Exploratory DCE-MRI showed no significant perfusion changes with aflibercept. CONCLUSION: Aflibercept 4mg/kg plus irinotecan-LV5FU2 every 2weeks had acceptable toxicity and pharmacokinetics, and showed promising antitumour activity.
ISSN: 0959-8049
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational MRI (+)
Clinical Digestive Oncology (+)
× corresponding author
# (joint) last author

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