57890
document
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 . 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 4 mg/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 ( 4 mg/kg ) on day 1 then irinotecan-LV5FU2 on days 1 and 2 . Subsequently , all patients received aflibercept with irinotecan-LV5FU2 every 2 weeks . 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 4 mg/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 > 3 months 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 4 mg/kg plus irinotecan-LV5FU2 every 2 weeks had acceptable toxicity and pharmacokinetics , and showed promising antitumour activity .
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Intervention_Pharmacological
aflibercept
57892
Intervention_Pharmacological
irinotecan , 5-fluorouracil and leucovorin
57893
Intervention_Pharmacological
aflibercept
57894
Intervention_Pharmacological
irinotecan , 5-fluorouracil and leucovorin ( LV5FU2 )
57895
Intervention_Control
placebo
57896
Intervention_Pharmacological
aflibercept
57897
Intervention_Pharmacological
irinotecan-LV5FU2
57898
Intervention_Pharmacological
aflibercept
57899
Intervention_Pharmacological
irinotecan-LV5FU2
57900
Intervention_Control
placebo
57901
Intervention_Pharmacological
aflibercept
57902
Intervention_Pharmacological
aflibercept
57903
Intervention_Pharmacological
aflibercept
57904
Outcome_Physical
median number of aflibercept cycles
57905
Outcome_Adverse-effects
neutropenia
57906
Outcome_Adverse-effects
fatigue
57907
Outcome_Adverse-effects
hypertension
57908
Participant_Condition
advanced solid tumours
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Participant_Condition
advanced solid tumours
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Participant_Sample-size
Twenty-seven