Medical Oncology Department, Universitat de Barcelona, IDIBELL, Institut Català d'Oncologia-L'Hospitalet, Barcelona, Spain.
Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain.
Int J Radiat Oncol Biol Phys. 2017 Mar 1;97(3):473-480. doi: 10.1016/j.ijrobp.2016.11.016. Epub 2016 Nov 17.
To evaluate the efficacy and safety of induction chemotherapy (IC) followed by bioradiotherapy (BRT) to achieve functional larynx preservation in the setting of locally advanced head and neck tumors.
This was a phase 2, open-label, multicenter study of patients with stage III and IVA laryngeal carcinoma who were candidates for total laryngectomy. The primary endpoint was the rate of survival with functional larynx (SFL) at 3 years, with a critical value to consider the study positive of SFL >59%. Patients received 3 cycles of IC with TPF (docetaxel, cisplatin, and 5-fluorouracil), and those who responded received conventional BRT with cetuximab. In patients with residual nodal disease after BRT, neck dissection was planned 2 months after BRT. Patients who did not respond to IC underwent total laryngectomy plus neck dissection and radiation therapy.
A total of 93 patients started TPF. Responses to IC on larynx target lesion were as follows: 37 patients (40%) showed a complete response; 38 patients (41%) showed a partial response; 8 patients (9%) showed stabilization; 2 patients (2%) showed progressive disease, and 8 patients (9%) were not evaluated (2 deaths, 5 adverse events, and 1 lost to follow-up). Seventy-three patients (78%) received BRT: 72 as per protocol, but 1 with only stable disease. Median follow-up was 53.7 months. Three-year actuarial rates were as follows: SFL: 70% (95% confidence interval [CI] 60%-79%); laryngectomy-free survival: 72% (95% CI 61%-81%); overall survival: 78% (95% CI: 63%-82%). The acute toxicity observed during both IC and BRT was as expected, with only 1 toxicity-related death (local bleeding) during BRT.
According to this protocol, the SFL rate was clearly higher than the critical value, with acceptable levels of toxicity. The use of cetuximab added to radiation therapy in patients with stage III and IVA laryngeal cancer who respond to TPF could improve functional larynx preservation. A phase 3 trial is warranted.
评估诱导化疗（IC）联合生物放疗（BRT）在局部晚期头颈部肿瘤患者中实现保留功能喉的疗效和安全性。
这是一项 2 期、开放标签、多中心研究，纳入了适合全喉切除术的 III 期和 IVA 期喉癌患者。主要终点为 3 年时具有功能保留喉（SFL）的生存率（SFL），临界值为 SFL>59%，考虑研究阳性。患者接受 3 个周期的 TPF（多西他赛、顺铂和 5-氟尿嘧啶）IC，对 IC 有反应的患者接受常规 BRT 联合西妥昔单抗。BRT 后有残留淋巴结疾病的患者计划在 BRT 后 2 个月行颈部清扫术。对 IC 无反应的患者行全喉切除术加颈部清扫术和放疗。
共有 93 例患者开始接受 TPF。IC 对喉靶病灶的反应如下：37 例（40%）完全缓解；38 例（41%）部分缓解；8 例（9%）稳定；2 例（2%）进展，8 例（9%）未评估（2 例死亡，5 例不良反应，1 例失访）。73 例（78%）患者接受了 BRT：72 例按方案接受治疗，但 1 例仅为稳定疾病。中位随访时间为 53.7 个月。3 年总生存率分别为：SFL：70%（95%可信区间[CI]：60%-79%）；无喉切除术生存：72%（95% CI：61%-81%）；总生存：78%（95% CI：63%-82%）。IC 和 BRT 期间观察到的急性毒性与预期相符，仅在 BRT 期间出现 1 例与毒性相关的死亡（局部出血）。
根据该方案，SFL 率明显高于临界值，且毒性可接受。在对 TPF 有反应的 III 期和 IVA 期喉癌患者中，西妥昔单抗联合放疗可提高保留功能喉的效果。需要开展 3 期临床试验。
