Details

Autor(en) / Beteiligte

• Cohen, Martin H.
• Chen, Huanyu
• Shord, Stacy
• Fuchs, Chana
• He, Kun
• Zhao, Hong
• Sickafuse, Sharon
• Keegan, Patricia
• Pazdur, Richard

Titel

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

Ist Teil von

• The oncologist (Dayton, Ohio), 2013-04, Vol.18 (4), p.460-466

Ort / Verlag

Durham, NC, USA: AlphaMed Press

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• Learning Objectives 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. 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 1–4) 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]: 0.64–0.98; 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: 0.46–0.72; p < .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: 1.50–3.60; p = .0001). Adverse reactions (≥25%) 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. 摘要 2011年11月7日，美国FDA批准了西妥昔单抗联合顺铂或卡铂和5‐氟尿嘧啶一线治疗复发性局部或转移性头颈鳞癌患者。这一批准是基于美国境外开展的一项随机试验，该试验纳入442例患者。治疗方案为第1天顺铂（100 mg/m2静脉输注）或卡铂（曲线下面积5，静脉输注），联合5‐氟尿嘧啶（第1 ∼ 4天1000 mg/m2/天持续静脉输注），3周为一个周期。西妥昔单抗起始剂量为400 mg/m2，继以250 mg/m2静脉输注，每周一次。完成计划的6治疗周期后，西妥昔单抗组疾病未进展的患者继续接受每周西妥昔单抗250 mg/m2治疗。该研究使用欧盟批准的西妥昔单抗剂量而非美国批准的剂量。一项在猴体内进行的药代动力学比较研究显示，与欧盟批准的西妥昔单抗剂量相比，美国批准的西妥昔单抗药物暴露高28%。西妥昔单抗组患者的主要有效性终点总生存获得显著改善[风险比（HR）：0.80；95%，可信区间（CI）：0.64 ∼ 0.98；p = 0.034，分层log‐rank检验）]。中位生存期分别为10.1和7.4个月。接受西妥昔单抗治疗的患者无进展生存期（PFS）也显著改善（HR：0.57；95%CI：0.46 ∼ 0.72；p < 0.0001）。中位PFS分别为5.5和3.3个月。缓解率为35.6%和19.5%（比值比：2.33；95%CI：1.50 ∼ 3.60； p = 0.0001）。西妥昔单抗联合化疗方案的不良反应（≥ 25%）包括恶心、贫血、呕吐、中性粒细胞减少、皮疹、无力、腹泻和食欲减退。西妥昔单抗组患者有10%发生结膜炎。其他不良反应（有时为严重不良反应）包括输注反应、低镁血症、低钙血症和低钾血症。The Oncologist 2013;18:460–466 The present cetuximab U.S. Food and Drug Administration submission seeks to expand the squamous cell head and neck cancer indication to include recurrent locoregional or metastatic disease. Cetuximab, in combination with platinum‐based therapy and 5‐fluorouracil (FU), is compared to platinum‐based therapy and 5‐FU alone.