Guigay J, Even C, Mayache-Badis L, Debbah M, Saada-Bouzid E, Tao Y, Deschamps F, Janot F, Lezghed N, Michel C
Department of Medical Oncology, Antoine Lacassagne Cancer Research Center, Nice, France.
Department of Head and Neck Cancer, Gustave Roussy, Villejuif, France.
Oral Oncol. 2017 May;68:114-118. doi: 10.1016/j.oraloncology.2017.03.009. Epub 2017 Mar 24.
Cetuximab, an anti-EGFR monoclonal antibody in combination with platinum and 5FU is the standard of care in first-line treatment of patients with recurrent head and neck squamous cell carcinoma (HNSCC), with an expected median outcome of 10months. For this population, development of efficacious and safer therapies is still needed.
A 62-year-old male with a first recurrence of human papillomavirus positive stage IVA (T3N2bM0) adenocarcinoma of the glossotonsillar sulcus not amenable to locoregional curative treatment was offered chemotherapy as part of the TPEx clinical trial. He was treated by cetuximab (loading dose 400mg/m on day 1 cycle 1, then 250mg/m weekly), and chemotherapy (cisplatin 75mg/m and docetaxel 75mg/m, on day 1). Cycles were repeated every 21days for 4 cycles (TPEx regimen) with systematic granulocyte colony-stimulating factor support at each cycle. Bi-monthly maintenance cetuximab 500mg/m was then administered. The patient showed a clinical complete response according to RECIST 1.1 criteria after 5months maintenance, with progression-free survival of 25months. Relapses that followed were treated with stereotactic irradiation, radiofrequency ablation, cetuximab and paclitaxel. The patient is alive eleven years after cancer diagnosis and remains controlled for his disease, with a cumulative period of 59months of cetuximab administration (equivalence of 121 injections).
This case report demonstrated that TPEx regimen, by synergistic interaction between taxanes and cetuximab, followed by bimonthly cetuximab maintenance may lead to patient complete remission within the first year of treatment. Furthermore, prolonged intermittent treatment with cetuximab seems to participate in the improved survival associated with preserved quality of life. Key favorable prognostic factors may be moderate tumor differentiation, oropharyngeal location, HPV p16 positive tumor status.
西妥昔单抗是一种抗表皮生长因子受体（EGFR）单克隆抗体，与铂类和5氟尿嘧啶联合使用是复发性头颈部鳞状细胞癌（HNSCC）患者一线治疗的标准方案，预期中位生存期为10个月。对于这一人群，仍需要开发更有效、更安全的治疗方法。
一名62岁男性，首次复发的人乳头瘤病毒阳性IVA期（T3N2bM0）舌扁桃体沟腺癌，无法进行局部根治性治疗，作为TPEx临床试验的一部分接受化疗。他接受了西妥昔单抗治疗（第1周期第1天负荷剂量400mg/m²，之后每周250mg/m²）以及化疗（第1天顺铂75mg/m²和多西他赛75mg/m²）。每21天重复1个周期，共4个周期（TPEx方案），每个周期均给予系统性粒细胞集落刺激因子支持。之后每两个月给予维持剂量西妥昔单抗500mg/m²。根据RECIST 1.1标准，患者在维持治疗5个月后显示临床完全缓解，无进展生存期为25个月。随后的复发采用立体定向放射治疗、射频消融、西妥昔单抗和紫杉醇治疗。该患者在癌症诊断后11年仍然存活，疾病得到控制，累计使用西妥昔单抗59个月（相当于121次注射）。
本病例报告表明，TPEx方案通过紫杉烷类与西妥昔单抗之间的协同作用，随后每两个月进行一次西妥昔单抗维持治疗，可能使患者在治疗的第一年内实现完全缓解。此外，延长西妥昔单抗间歇治疗似乎有助于提高生存率并保持生活质量。关键的有利预后因素可能是肿瘤中度分化、口咽部位、HPV p16阳性肿瘤状态。
