Szturz Petr, Vermorken Jan B
Medical Oncology, Department of Oncology, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium.
Oral Oncol. 2020 Feb;101:104492. doi: 10.1016/j.oraloncology.2019.104492. Epub 2019 Dec 11.
In recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN), the armamentarium of systemic anti-cancer modalities continues to grow in parallel with innovations in and better integration of local approaches. The backbone of cytotoxic chemotherapy remains cisplatin with 5-fluorouracil or a taxane. In contrast to cisplatin, the tumoricidal activity of carboplatin monotherapy is debatable. Adding the epidermal growth factor receptor (EGFR) inhibitor cetuximab to a platinum/5-fluorouracil doublet (the so-called EXTREME regimen) produced a statistically but also clinically significant improvement of survival and became thus the standard first-line palliative treatment in adequately fit patients. Interestingly, three large randomized trials (EXTREME, SPECTRUM, and ZALUTE) evaluating different anti-EGFR monoclonal antibodies (cetuximab, panitumumab, and zalutumumab, respectively) demonstrated preferential anti-tumour efficacy in patients with primary cancer in the oral cavity. Modern immunotherapy with immunomodulating antibodies, dubbed immune checkpoint inhibitors, such as anti-programmed cell death protein-1 (anti-PD-1) inhibitors nivolumab and pembrolizumab, showed unprecedented activity in one first-line (KEYNOTE-048) and several second-line trials (CheckMate-141, KEYNOTE-012, KEYNOTE-055, and KEYNOTE-040). In a minority of also heavily-pretreated patients, these agents generate long-lasting responses without the typical chemotherapy-related toxicity, however, at a price of a low overall response rate, rare but potentially life-threatening immune-related adverse events, the risk of hyperprogression, and high costs. In oligometastatic disease, emerging data indicate long-term benefit with locally ablative techniques including metastasectomy and stereotactic radiotherapy of pulmonary but also hepatic and other distant lesions. In the frame of highly-individualized cancer care, a particularly intriguing approach is a combination of systemic and local therapies.
在复发性和/或转移性头颈部鳞状细胞癌（R/M-SCCHN）中，全身抗癌治疗手段不断增加，同时局部治疗方法也有创新并得到更好整合。细胞毒性化疗的主要药物仍是顺铂联合5-氟尿嘧啶或紫杉烷。与顺铂不同，卡铂单药的杀瘤活性存在争议。在铂类/5-氟尿嘧啶双药方案（即所谓的EXTREME方案）中加入表皮生长因子受体（EGFR）抑制剂西妥昔单抗，在统计学上以及临床上均显著提高了生存率，因此成为身体状况良好患者的标准一线姑息治疗方案。有趣的是，三项大型随机试验（EXTREME、SPECTRUM和ZALUTE）分别评估了不同的抗EGFR单克隆抗体（西妥昔单抗、帕尼单抗和扎鲁单抗），结果显示对口腔原发性癌患者具有优先的抗肿瘤疗效。使用免疫调节抗体的现代免疫疗法，即所谓的免疫检查点抑制剂，如抗程序性细胞死亡蛋白1（抗PD-1）抑制剂纳武单抗和派姆单抗，在一项一线试验（KEYNOTE-048）和多项二线试验（CheckMate-141、KEYNOTE-012、KEYNOTE-055和KEYNOTE-040）中显示出前所未有的活性。在少数经过大量预处理的患者中，这些药物可产生持久反应，且无典型的化疗相关毒性，然而，其代价是总体缓解率较低、罕见但可能危及生命的免疫相关不良事件、疾病快速进展的风险以及高昂的成本。在寡转移疾病中，新出现的数据表明，包括肺转移灶切除术和立体定向放射治疗以及肝和其他远处转移灶的局部消融技术可带来长期益处。在高度个体化的癌症治疗框架下，一种特别引人关注的方法是全身治疗与局部治疗相结合。
