Radiation Oncology Department, University Hospital, CHRU, Brest, France.
Clinical Investigation Center INSERM 1412, Biostatistics Unit, University Hospital, Brest, France.
Target Oncol. 2017 Aug;12(4):505-512. doi: 10.1007/s11523-017-0499-0.
Cetuximab, a chimeric monoclonal antibody against EGFR sensitizes tumors to radiotherapy (RT), but is associated with skin and mucosal toxicity.
We report outcomes and tolerance of definitive RT in association with cetuximab in patients with locally advanced squamous cell carcinoma (LASCC) of the head and neck.
Between 2006 and 2011, 92 consecutive patients with LASCC of the head and neck were treated with RT and concomitant weekly cetuximab. Median age was 61.7 years. Most patients presented with oropharyngeal tumors (52.2%) and stage IV disease (77.2%).
Sixty-nine patients received at least 7 cycles of cetuximab. Cetuximab was stopped at the first infusion following allergic reactions in four patients. During RT, 37% of patients developed grade ≥ 3 dermatitis; grade ≥ 2 cetuximab-induced rash occurred in 43 patients (46.7%). Severe mucositis (grade ≥ 3) affected 57.6% of patients. Ten percent of patients did not receive the full course of RT, and temporary discontinuation due to acute toxicity was frequent and affected 37 patients (53%). The median RT overall treatment time (OTT) in patients with interrupted RT was 56 days (47-75) compared to 51 days (47-65) in patients who did not require toxicity-related radiation interruptions (p < 0.05). After a median follow-up of 17.5 months (1.3-107.6) for all patients, median overall survival was 17.9 months (95% CI: 12.7-23.2), and loco-regional control (LRC) was 9.2 months (95% CI: 3.9-14.4). On multivariate analysis, hemoglobin concentration and occurrence of rash grade ≥ 2 were independent prognostic factors for LRC (p = 0.023 and p = 0.006, respectively). Lack of rash and extended OTT negatively impacted overall survival (p = 0.048 and 0.052, respectively).
Skin and mucosal toxicity remains an issue in patients with LASCC of the head and neck treated with concomitant cetuximab and RT. Severe toxicity leads to treatment interruptions and prolonged overall treatment time, with consequent decreased overall survival in these patients.
西妥昔单抗是一种针对 EGFR 的嵌合单克隆抗体，可使肿瘤对放射治疗（RT）敏感，但与皮肤和黏膜毒性有关。
我们报告了在头颈部局部晚期鳞状细胞癌（LASCC）患者中，与 Cetuximab 联合使用根治性 RT 的结果和耐受性。
2006 年至 2011 年间，92 例头颈部 LASCC 患者接受了 RT 和每周一次的 Cetuximab 联合治疗。中位年龄为 61.7 岁。大多数患者有口咽肿瘤（52.2%）和 IV 期疾病（77.2%）。
69 例患者至少接受了 7 个周期的 Cetuximab。4 例患者因过敏反应在第一次输注时停止使用 Cetuximab。在 RT 期间，37%的患者出现 3 级及以上皮炎；43 例（46.7%）患者出现 2 级及以上 Cetuximab 诱导皮疹。57.6%的患者出现严重粘膜炎（3 级及以上）。10%的患者未接受完整的 RT 疗程，因急性毒性而暂时中断治疗的情况很常见，有 37 例（53%）患者出现这种情况。中断 RT 的患者中位 RT 总治疗时间（OTT）为 56 天（47-75），而无需因毒性相关中断 RT 的患者中位 OTT 为 51 天（47-65）（p<0.05）。所有患者中位随访 17.5 个月（1.3-107.6）后，中位总生存期为 17.9 个月（95%CI：12.7-23.2），局部区域控制率（LRC）为 9.2 个月（95%CI：3.9-14.4）。多因素分析显示，血红蛋白浓度和皮疹 2 级以上的发生是 LRC 的独立预后因素（p=0.023 和 p=0.006）。无皮疹和延长 OTT 对总生存期有负面影响（p=0.048 和 0.052）。
头颈部 LASCC 患者接受 Cetuximab 和 RT 联合治疗时，皮肤和黏膜毒性仍然是一个问题。严重的毒性导致治疗中断和总治疗时间延长，从而降低了这些患者的总生存率。
