已有回顾性研究表明，与其他患者相比，使用二甲双胍的头颈部鳞状细胞癌（HNSCC）患者表现出更好的生存率。我们旨在确定二甲双胍与化疗放疗相结合是否能改善HNSCC患者的生存率，与历史对照组进行比较。我们在新诊断的HNSCC患者中进行了一项I/II期单臂临床试验（NCT02949700）。患者在放疗期间接受基于铂的化疗放疗，同时口服二甲双胍，剂量分别为850 mg BID或1500 mg BID，在放疗前进行为期2周的前导期。在整个研究期间，我们确定了毒性反应、疾病反应和生存指标。共有25名患者对毒性和生存进行了评估；其中9名患者未能达到预定的70％用药遵从度。在I期中未发现剂量限制性毒性，而在整个研究期间，与二甲双胍相关的4级不良事件也未出现。II期中的主要结果显示，响应率为96％。在符合协议的p16 +亚组中，3年总生存率约为70％，而在符合协议的p16-亚组中为0％。在二甲双胍遵从度大于等于70％和二甲双胍遵从度小于70％的参与者中，二甲双胍遵从度大于等于70％的队列中的生存状况表明了一种趋势的改善，尽管这种差异并不显著。在HNSCC患者中，二甲双胍在同时化疗放疗期间耐受性良好。它作为化疗放射敏化剂的有效性尚不明确，需要进一步进行随机对照的临床试验来研究这一患者群体。版权所有© 2023 Elsevier Ltd.。保留所有权利。

Retrospective studies have shown that head and neck squamous cell carcinoma (HNSCC) patients taking metformin demonstrate superior survival compared to their counterparts. We sought to determine whether metformin combined with chemoradiation would improve HNSCC patient survival compared to historical controls.We conducted a Phase I/II prospective, single arm clinical trial in patients with newly diagnosed HNSCC (NCT02949700). Patients received platinum-based chemoradiation in combination with orally dosed metformin at one of 2 doses- 850 mg BID or 1500 mg BID administered during radiation, with a 2-week lead-in phase. Toxicity, disease response and survival metrics were ascertained throughout the study period.A total of 25 patients were evaluable for toxicity and survival; 9 failed to reach the predetermined 70% compliance with the study drug. No dose limiting toxicities were identified in the Phase I component and there were no grade 4 adverse events likely related to metformin throughout the study. The primary outcome for the Phase II component was met with a response rate of 96%. Three-year overall survival was ∼70% in the per protocol p16 + cohort and 0% in the per protocol p16- cohort. Survival among participants with a ≥70% metformin compliance to <70% metformin compliance demonstrated a trend towards improvement in the ≥70% compliance cohort, though this did not reach significance.Metformin is well tolerated during concurrent chemoradiation for HNSCC. Its effectiveness as a chemo-radiosensitizer remains unclear and will require further study with randomized controlled clinical trials in this patient population.Copyright © 2023 Elsevier Ltd. All rights reserved.