Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Department of Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Cancer Biol Med. 2023 Jun 22;20(6):465-76. doi: 10.20892/j.issn.2095-3941.2022.0762.
This study was aimed at analyzing the efficacy and safety of an injectable form of chlorogenic acid (CGA) in patients with recurrent high-grade glioma after standard of care treatments, through a first-in-human, open-label, dose-escalation phase I trial.
A total of 26 eligible patients were enrolled, received intramuscular CGA injections at 5 dose levels, and were followed up for 5 years. CGA was well tolerated, and the maximum tolerated dose was 5.5 mg/kg.
The most common treatment-related adverse events occurred at the sites of injection. No grade 3 or 4 adverse events (e.g., drug allergy) were reported for these patients except for induration at the injection sites. A clinical pharmacokinetic study showed that CGA was rapidly eliminated from the plasma, with a t of 0.95-1.27 h on day 1 and 1.19-1.39 h on day 30, and no detectable CGA was observed on days 9, 11, 13, 23, 25, 27, and 29 before CGA administration. After the first treatment cycle, 52.2% of patients (12 of 23) achieved stable disease. Long-term follow-up indicated an estimated median overall survival of 11.3 months for all 23 evaluable patients. Of the 18 patients with grade 3 glioma, the median overall survival was 9.5 months. Two patients remained alive at the cutoff day.
This phase I study demonstrated that CGA has a favorable safety profile (with no severe toxicity), and provides preliminary clinical benefits for patients with high grade glioma relapsing after prior standard therapies, thus shedding light on the potential clinical application of CGA for recurrent grade 4 glioma.
本研究旨在通过首例人体、开放标签、剂量递增的 I 期试验，分析在接受标准治疗后复发的高级别胶质瘤患者中使用可注射形式的绿原酸（CGA）的疗效和安全性。
共纳入 26 名符合条件的患者，肌肉注射 CGA 注射液，共 5 个剂量水平，并随访 5 年。CGA 具有良好的耐受性，最大耐受剂量为 5.5mg/kg。
最常见的治疗相关不良事件发生在注射部位。除注射部位硬结外，这些患者未报告任何 3 或 4 级不良事件（如药物过敏）。一项临床药代动力学研究表明，CGA 从血浆中迅速消除，第 1 天的 t 为 0.95-1.27 小时，第 30 天的 t 为 1.19-1.39 小时，在 CGA 给药前第 9、11、13、23、25、27 和 29 天未检测到 CGA。第一个治疗周期后，52.2%（12/23）的患者达到稳定疾病。长期随访显示，所有 23 名可评估患者的总生存期估计中位数为 11.3 个月。在 18 名 3 级胶质瘤患者中，总生存期中位数为 9.5 个月。两名患者在截止日期仍存活。
这项 I 期研究表明，CGA 具有良好的安全性（无严重毒性），并为接受标准治疗后复发的高级别胶质瘤患者提供了初步的临床获益，从而为 CGA 治疗复发性 4 级胶质瘤的潜在临床应用提供了依据。
