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10.1172/jci.insight.90380 http://scihub22266oqcxt.onion/10.1172/jci.insight.90380 C5396533!5396533 !28422758     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28422758 &cmd=llinks): Failed to open stream: HTTP request failed! 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First-in-human trial of multikinase VEGF inhibitor regorafenib and anti-EGFR antibody cetuximab in advanced cancer patients |pdf=|usr=}}{{28422758 }} gab.com Text First-in-human trial of multikinase VEGF inhibitor regorafenib and anti-EGFR antibody cetuximab in advanced cancer patients JO: JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=28422758 #FOAvip BACKGROUND: The combination of multikinase VEGF inhibitor regorafenib and anti-EGFR antibody cetuximab overcomes intrinsic and acquired resistance in both EGFR-sensitive and EGFR-resistant preclinical models of colorectal cancer (CRC). METHODS: Utilizing a standard 3+3 design, a phase I study was designed to determine safety, maximum tolerated dose (MTD), and dose-limiting toxicities (DLTs) of the regorafenib plus cetuximab combination among patients with advanced cancer including CRC. Comprehensive genomic profiling was performed on the exceptional responder. RESULTS: Among the 27 patients enrolled the median age was 54 years. None of 19 patients treated at dose level 1 (cetuximab i.v. 200 mg/m2 followed by 150 mg/m2 weekly + regorafenib 80 mg daily) experienced a DLT, and 2 of 5 patients treated at dose level 2 (cetuximab i.v. 200 mg/m2 followed by 150 mg/m2 weekly + regorafenib 120 mg daily) experienced a DLT (grade 3 thrombocytopenia [n = 1] and grade 3 intra-abdominal bleed [n = 1]). Most common adverse events were grade 1 or 2 rash (20 patients). Of 24 evaluable patients, 11 (46%) patients had clinical benefit (stable disease > 6 cycles or partial response [PR]) (CRC n = 8, one patient each with head and neck cancer, carcinoma of unknown primary, and glioblastoma). A CRC patient, who progressed on anti-EGFR and regorafenib, achieved a PR (46% decrease per RECIST v1.1) lasting 15 months. Genomic profiling of an exceptional responder with response for over 27 cycles revealed hypermutated genotype with microsatellite instability (MSI). CONCLUSION: Regorafenib 80 mg daily plus cetuximab 200 mg/m2 loading dose, followed by 150 mg/m2 every week is the MTD/recommended phase II dose. The combination demonstrated early signals of activity in wild-type CRC, including 1 exceptional responder with MSI high. TRIAL REGISTRATION: clinicaltrials.gov NCT02095054FUNDING. The University of Texas MD Anderson Cancer Center is supported by the NIH Cancer Center Support Grant CA016672. This work was supported in part by the Cancer Prevention Research Institute of Texas grant RP110584 and National Center for Advancing Translational Sciences grant UL1 TR000371 (Center for Clinical and Translational Sciences). Twit Text FOAVip First-in-human trial of multikinase VEGF inhibitor regorafenib and anti-EGFR antibody cetuximab in advanced cancer patients ????JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=28422758 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28422758 #FOAvip English Wikipedia <ref>{{Cite pmid|28422758 }}</ref> First-in-human trial of multikinase VEGF inhibitor regorafenib and anti-EGFR antibody cetuximab in advanced cancer patients #MMPMID28422758 Subbiah V ; Khawaja MR ; Hong DS ; Amini B ; Yungfang J ; Liu H ; Johnson A ; Schrock AB ; Ali SM ; Sun JX ; Fabrizio D ; Piha-Paul S ; Fu S ; Tsimberidou AM ; Naing A ; Janku F ; Karp DD ; Overman M ; Eng C ; Kopetz S ; Meric-Bernstam F ; Falchook GS JCI Insight 2017[Apr]; 2 (8 ): ä PMID28422758 show ga BACKGROUND: The combination of multikinase VEGF inhibitor regorafenib and anti-EGFR antibody cetuximab overcomes intrinsic and acquired resistance in both EGFR-sensitive and EGFR-resistant preclinical models of colorectal cancer (CRC). METHODS: Utilizing a standard 3+3 design, a phase I study was designed to determine safety, maximum tolerated dose (MTD), and dose-limiting toxicities (DLTs) of the regorafenib plus cetuximab combination among patients with advanced cancer including CRC. Comprehensive genomic profiling was performed on the exceptional responder. RESULTS: Among the 27 patients enrolled the median age was 54 years. None of 19 patients treated at dose level 1 (cetuximab i.v. 200 mg/m2 followed by 150 mg/m2 weekly + regorafenib 80 mg daily) experienced a DLT, and 2 of 5 patients treated at dose level 2 (cetuximab i.v. 200 mg/m2 followed by 150 mg/m2 weekly + regorafenib 120 mg daily) experienced a DLT (grade 3 thrombocytopenia [n = 1] and grade 3 intra-abdominal bleed [n = 1]). Most common adverse events were grade 1 or 2 rash (20 patients). Of 24 evaluable patients, 11 (46%) patients had clinical benefit (stable disease > 6 cycles or partial response [PR]) (CRC n = 8, one patient each with head and neck cancer, carcinoma of unknown primary, and glioblastoma). A CRC patient, who progressed on anti-EGFR and regorafenib, achieved a PR (46% decrease per RECIST v1.1) lasting 15 months. Genomic profiling of an exceptional responder with response for over 27 cycles revealed hypermutated genotype with microsatellite instability (MSI). CONCLUSION: Regorafenib 80 mg daily plus cetuximab 200 mg/m2 loading dose, followed by 150 mg/m2 every week is the MTD/recommended phase II dose. The combination demonstrated early signals of activity in wild-type CRC, including 1 exceptional responder with MSI high. TRIAL REGISTRATION: clinicaltrials.gov NCT02095054FUNDING. The University of Texas MD Anderson Cancer Center is supported by the NIH Cancer Center Support Grant CA016672. This work was supported in part by the Cancer Prevention Research Institute of Texas grant RP110584 and National Center for Advancing Translational Sciences grant UL1 TR000371 (Center for Clinical and Translational Sciences). äFirst-in-human trial of multikinase VEGF inhibitor regorafenib and ant(epmc).pdf DeepDyve Pubget Overpricing