{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:37:21Z","timestamp":1788871041596,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2014,8,7]],"date-time":"2014-08-07T00:00:00Z","timestamp":1407369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2014,12,15]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Platinum\u2010based therapy combined with cetuximab is standard first\u2010line therapy for recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN). Preclinical studies have suggested that mammalian target of rapamycin inhibitors may overcome resistance to epidermal growth factor receptor blockers and may augment cetuximab antitumor activity. We conducted a phase 1b trial of carboplatin, cetuximab, and everolimus for untreated RMSCCHN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Patients received carboplatin (area under the curve\u2009=\u20092 mg\/ml\/min; 3 weeks on, 1 week off), cetuximab (with a loading dose of 400 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      and then 250 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      weekly), and dose\u2010escalating everolimus (2.5, 5.0, 7.5, and 10 mg\/day) with a 3+3 design. After 4 cycles, patients without progression continued cetuximab\/everolimus until progression or intolerable toxicity. Patients (age\u2009\u2265\u200918 years) had previously untreated, unresectable RMSCCHN not amenable to radiotherapy and an Eastern Cooperative Oncology Group performance status of 0 to 2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The study enrolled 20 patients (male\/female\u2009=\u200918\/2) with RMSCCHN; the median age was 65 years (44\u201075 years). Thirteen patients received everolimus (male\/female\u2009=\u200992%). Two of 6 patients receiving 2.5 mg\/day experienced dose\u2010limiting toxicity (DLT) with grade 3 hyponatremia and nausea. In 7 patients receiving de\u2010escalated everolimus (2.5 mg every other day), grade 3 hyperglycemia produced DLT in 1 of 6 patients. The objective response rate (RR) was 61.5% (all partial responses). Progression\u2010free survival (PFS) was 8.15 months. The pharmacokinetics of everolimus was described with a 2\u2010compartment mixed\u2010effects model. There was a significant correlation between tumor p\u2010p44\/42 staining and response (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.044) and a marginally significant correlation between phosphorylated mammalian target of rapamycin and overall survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>\n                      The maximum tolerated dose of everolimus with cetuximab and carboplatin was 2.5 mg every other day. The regimen was associated with an encouraging RR and PFS, and this suggested possible clinical efficacy in a select group of patients with squamous cell carcinoma of the head and neck.\n                      <jats:bold>\n                        <jats:italic>Cancer<\/jats:italic>\n                        2014;120:3940\u20133951.\n                      <\/jats:bold>\n                      \u00a9\n                      <jats:italic>2014 American Cancer Society<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.28965","type":"journal-article","created":{"date-parts":[[2014,8,7]],"date-time":"2014-08-07T12:45:06Z","timestamp":1407415506000},"page":"3940-3951","source":"Crossref","is-referenced-by-count":45,"title":["Phase 1 and pharmacokinetic study of everolimus in combination with cetuximab and carboplatin for recurrent\/metastatic squamous cell carcinoma of the head and neck"],"prefix":"10.1002","volume":"120","author":[{"given":"Nabil F.","family":"Saba","sequence":"first","affiliation":[{"name":"Winship Cancer Institute, Department of Hematology and Medical Oncology Emory University School of Medicine  Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selwyn J.","family":"Hurwitz","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemical Pharmacology, Center for AIDS Research, Department of Pediatrics Emory University School of Medicine  Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Magliocca","sequence":"additional","affiliation":[{"name":"Department of Pathology Emory University School of Medicine  Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungjin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Emory School of Public Health  Atlanta 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Emory School of Public Health  Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackie","family":"Rogerio","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals East Hanover New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Mendel","sequence":"additional","affiliation":[{"name":"UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Kono","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Littleton Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen","family":"Lewis","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute, Department of Hematology and Medical Oncology Emory University School of Medicine  Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy Y.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Winship Cancer Institute Emory University School of Medicine  Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Higgins","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Winship Cancer Institute Emory University School of Medicine  Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"El\u2010Deiry","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Winship Cancer Institute Emory University School of Medicine  Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trad","family":"Wadsworth","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Winship Cancer Institute Emory University School of Medicine  Atlanta 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