{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:44:40Z","timestamp":1790786680463,"version":"4.1.0"},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Learning Objectives<\/jats:title>\n                  <jats:p>Compare survival outcomes among patients with SCCHN treated with a platinum\/5 -FU regimen with and without cetuximab. Compare adverse event profiles among patients with SCCHN treated with a platinum\/5 -FU regimen with and without cetuximab. Describe potential risk-benefit issues identified in the EU and US studies.<\/jats:p>\n                  <jats:p>On November 7, 2011, the U.S. Food and Drug Administration approved cetuximab in combination with cisplatin or carboplatin and 5-fluorouracil for the first-line treatment of patients with recurrent locoregional or metastatic squamous cell head and neck cancer. Approval was based on a randomized study of 442 patients conducted outside the U.S. Cisplatin (100 mg\/m2 intravenously) or carboplatin (area under the curve 5 intravenously) on day 1 with 5-fluorouracil (1,000 mg\/m2\/day continuous intravenous infusion days 1\u20134) were administered every 3 weeks. Cetuximab, 400 mg\/m2 intravenously, was administered initially followed by cetuximab, 250 mg\/m2 intravenously weekly. After completion of six planned treatment courses, cetuximab patients without progression continued cetuximab 250 mg\/m2 weekly. The study used European Union (EU)-approved cetuximab rather than U.S.-approved cetuximab. U.S.-approved cetuximab provides approximately 28% higher exposure relative to EU-approved cetuximab in a pharmacokinetic comparability study in monkeys. Overall survival, the primary efficacy endpoint, was significantly improved in cetuximab-treated patients (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.64\u20130.98; p = .034, stratified log-rank test). Median survival times were 10.1 and 7.4 months, respectively. Progression-free survival (PFS) was also significantly improved in patients receiving cetuximab (HR: 0.57; 95% CI: 0.46\u20130.72; p &amp;lt; .0001). Median PFS times were 5.5 and 3.3 months, respectively. Response rates were 35.6% and 19.5% (odds ratio: 2.33; 95% CI: 1.50\u20133.60; p = .0001). Adverse reactions (\u226525%) from cetuximab plus chemotherapy treatment included nausea, anemia, vomiting, neutropenia, rash, asthenia, diarrhea, and anorexia. Conjunctivitis occurred in 10% of cetuximab patients. Other adverse reactions, sometimes severe, included infusion reactions, hypomagnesemia, hypocalcemia, and hypokalemia.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.2012-0458","type":"journal-article","created":{"date-parts":[[2013,4,11]],"date-time":"2013-04-11T04:15:13Z","timestamp":1365653713000},"page":"460-466","source":"Crossref","is-referenced-by-count":50,"title":["Approval Summary: Cetuximab in Combination With Cisplatin or Carboplatin and 5-Fluorouracil for the First-Line Treatment of Patients With Recurrent Locoregional or Metastatic Squamous Cell Head and Neck Cancer"],"prefix":"10.1093","volume":"18","author":[{"given":"Martin H.","family":"Cohen","sequence":"first","affiliation":[{"name":"Office of Hematology Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, 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