TY - JOUR
T1 - Phase II trial of single-agent foretinib (GSK1363089) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck
AU - Seiwert, Tanguy
AU - Sarantopoulos, John
AU - Kallender, Howard
AU - McCallum, Stewart
AU - Keer, Harold N.
AU - Blumenschein, George
N1 - Funding Information:
Acknowledgments Funding for this study was provided by GlaxoS-mithKline (NCT00725764). All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. Editorial support in the form of copyediting, development of a draft outline, assembling tables and figures, collating author comments and referencing was provided by Jim Kesslick of CONNEXION Healthcare, Newtown, PA and MediTech Media, Manchester, UK, funded by GlaxoSmithKline. Grant support for MET-related research was provided from a Flight Attendant Medical Research Institute (FAMRI) Young Clinical Scientist Award (T.Y. Seiwert).
PY - 2013/4
Y1 - 2013/4
N2 - Summary: Background Foretinib is a small-molecule, oral multikinase inhibitor primarily targeting the mesenchymal epithelial transition (MET) factor receptor, and the vascular endothelial growth factor receptor 2. We conducted a phase II study to evaluate the single-agent activity and tolerability of foretinib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). Methods An open-label, single-arm, multicenter trial employing a Simon 2-stage design was conducted with a total of 41 patients planned for the study. One or more responses in the first 14 patients were required in order to progress to the second stage. Foretinib was administered as 240 mg orally for 5 consecutive days of a 14-day treatment cycle (5/9 schedule) to patients with recurrent and/or metastatic SCCHN. Results Fourteen patients were enrolled. The study did not meet criteria for continuing to the second stage. A maximum of 30 cycles were administered (median = 4.0). Fifty percent of patients (7/14) showed stable disease (SD), 43 % of patients (6/14) experienced tumor shrinkage and two patients had prolonged disease stabilization for ≥13 months. The most common adverse events were fatigue, constipation and hypertension, which were manageable with additional medication or adjustments to the dosing schedule. Conclusion Foretinib 240 mg on a 5/9 schedule was generally well tolerated. SD was the best-observed outcome, with minor tumor shrinkage detected in nearly half of all patients. The efficacy results, prolonged disease stabilization and tolerable side-effect profile, support further investigation, possibly in combination with other targeted agents or cytotoxic chemotherapy for SCCHN.
AB - Summary: Background Foretinib is a small-molecule, oral multikinase inhibitor primarily targeting the mesenchymal epithelial transition (MET) factor receptor, and the vascular endothelial growth factor receptor 2. We conducted a phase II study to evaluate the single-agent activity and tolerability of foretinib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). Methods An open-label, single-arm, multicenter trial employing a Simon 2-stage design was conducted with a total of 41 patients planned for the study. One or more responses in the first 14 patients were required in order to progress to the second stage. Foretinib was administered as 240 mg orally for 5 consecutive days of a 14-day treatment cycle (5/9 schedule) to patients with recurrent and/or metastatic SCCHN. Results Fourteen patients were enrolled. The study did not meet criteria for continuing to the second stage. A maximum of 30 cycles were administered (median = 4.0). Fifty percent of patients (7/14) showed stable disease (SD), 43 % of patients (6/14) experienced tumor shrinkage and two patients had prolonged disease stabilization for ≥13 months. The most common adverse events were fatigue, constipation and hypertension, which were manageable with additional medication or adjustments to the dosing schedule. Conclusion Foretinib 240 mg on a 5/9 schedule was generally well tolerated. SD was the best-observed outcome, with minor tumor shrinkage detected in nearly half of all patients. The efficacy results, prolonged disease stabilization and tolerable side-effect profile, support further investigation, possibly in combination with other targeted agents or cytotoxic chemotherapy for SCCHN.
KW - Foretinib
KW - Head and neck cancer
KW - Phase II study
KW - VEGFR2
KW - c-MET
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U2 - 10.1007/s10637-012-9861-3
DO - 10.1007/s10637-012-9861-3
M3 - Article
C2 - 22918720
AN - SCOPUS:84879554465
SN - 0167-6997
VL - 31
SP - 417
EP - 424
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 2
ER -