Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York, USA.
Cancer. 2011 Jul 15;117(14):3173-81. doi: 10.1002/cncr.25786. Epub 2011 Jan 18.
Concurrent inhibition of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) is an active and well tolerated regimen in recurrent head and neck cancer (HNC). In the current phase 1 trial, the authors sought to determine the maximum tolerated dose (MTD) and efficacy of concurrent erlotinib and celecoxib as a radiosensitizing regimen.
Fourteen patients with previously irradiated HNC with no distant metastases who required reirradiation were eligible. Treatment consisted of daily erlotinib 150 mg and twice daily celecoxib (escalated from 200 mg to 600 mg using a 3 + 3 design with an expanded cohort at the MTD) starting on Day 1 and was continued during radiation. Daily radiation was started on Day 15, and maintenance erlotinib was recommended.
The recommended phase 2 dose of celecoxib was 400 mg. Three dose-limiting toxicities included late in-field orocutaneous fistula (Dose Level 2), osteonecrosis (Dose Level 3), and trismus (Dose Level 3). Acute grade ≥ 3 toxicities were uncommon and included mucositis (21%) and dermatitis (14%). At a median follow-up of 11 months, the 1-year locoregional control, progression-free survival, and overall survival rates were 60%, 37%, and 55%, respectively.
Concurrent erlotinib, celecoxib, and reirradiation was a feasible and clinically active regimen in a population of patients with recurrent HNC who had a poor prognosis.
表皮生长因子受体（EGFR）和环氧化酶-2（COX-2）的同时抑制是复发性头颈部癌症（HNC）的一种积极且耐受良好的治疗方案。在当前的 1 期试验中，作者旨在确定同时使用厄洛替尼和塞来昔布作为放射增敏方案的最大耐受剂量（MTD）和疗效。
14 名先前接受过放疗且无远处转移的复发性 HNC 患者符合条件。治疗包括每天口服厄洛替尼 150mg 和塞来昔布（每天 2 次，剂量从 200mg 逐步增加至 600mg，采用 3+3 设计，在 MTD 时扩大队列），从第 1 天开始，并在放疗期间持续进行。第 15 天开始每天进行放疗，并建议维持厄洛替尼治疗。
推荐的塞来昔布 2 期剂量为 400mg。3 种剂量限制毒性包括晚期场内口咽瘘（剂量水平 2）、骨坏死（剂量水平 3）和牙关紧闭（剂量水平 3）。急性≥3 级毒性并不常见，包括粘膜炎（21%）和皮炎（14%）。在中位随访 11 个月时，1 年局部区域控制、无进展生存期和总生存期的率分别为 60%、37%和 55%。
厄洛替尼、塞来昔布和再放疗在复发性 HNC 患者中是一种可行且具有临床活性的方案，这些患者预后不良。
