Hematology Oncology Section, Medical Care Line, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, United States; Department of Internal Medicine, Section of Hematology/Oncology, Baylor College of Medicine, Houston, TX, United States.
Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, United States.
Oral Oncol. 2023 Oct;145:106536. doi: 10.1016/j.oraloncology.2023.106536. Epub 2023 Aug 8.
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.
回顾性研究表明，服用二甲双胍的头颈部鳞状细胞癌（HNSCC）患者的生存情况优于未服用二甲双胍的患者。我们旨在确定二甲双胍联合放化疗是否比历史对照患者的生存情况有所改善。
我们开展了一项新诊断的 HNSCC 患者的 I/II 期前瞻性、单臂临床试验（NCT02949700）。患者接受铂类为基础的放化疗联合口服二甲双胍治疗，2 种剂量方案：850mg，每日 2 次（BID）或 1500mg，BID，在放化疗前进行 2 周的导入期。整个研究期间都评估了毒性、疾病反应和生存指标。
共有 25 名患者可评估毒性和生存情况；9 名患者未能达到研究药物 70%的预定依从率。I 期部分未发现剂量限制性毒性，整个研究过程中未发生任何与二甲双胍相关的 4 级不良事件。II 期部分的主要终点是反应率达到 96%。在符合方案的 p16+队列中，3 年总生存率约为 70%，在符合方案的 p16-队列中则为 0%。在二甲双胍依从性≥70%的患者中，与二甲双胍依从性<70%的患者相比，生存情况有改善的趋势，但未达到统计学意义。
二甲双胍在 HNSCC 同期放化疗中耐受性良好。作为化疗增敏剂的效果仍不清楚，需要在该患者人群中进行随机对照临床试验进一步研究。
