Li Su, Bi Bingtian, Luo Guangyu, Zhan Jing, Zhang Rong, Li Jibin, Chen Naisheng, Huang Jinling, Xue Jinping, Xu Guoliang
State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Department of Clinical Trial Center, Cancer Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China.
Cancer Chemother Pharmacol. 2020 Aug;86(2):267-276. doi: 10.1007/s00280-020-04096-y. Epub 2020 Jul 24.
Photodynamic therapy (PDT) schedules are based on sensitiser dose, light dose, and drug-light interval. The aim of the phase Ι study was to choose optimal dose and drug-light interval for PDT with photocyanine using pharmacokinetics (PK) and pharmacodynamics (PD).
Twenty-eight cancer patients were enrolled. In trial A, 12 patients received one of four ascending doses of photocyanine intravenously 24 h prior to 180-270 J/cm illumination. 0.2 mg/kg dose was infused to ten patients 12-48 h prior to 120 J/cm illumination in trial B. In trial C, 0.1 mg/kg dose was infused to six patients 6 or 12 h prior to 180-270 J/cm illumination. Serum concentrations of photocyanine were measured, and simulations were performed to assess the effect of drug exposure in tissue on responses.
Analysis of photocyanine levels of patients indicated that the two-compartment model best fit the data. Simulations showed that the rates of the drug entering tissues and leaving tissues were equal at 8-12 h after injection. Patients experienced pain which was related to photocyanine serum levels, especially with serum levels above 2500 ng/ml. Fewer non-responders were observed at serum levels higher than 1000 ng/ml for illumination at least 12 h after administration.
It is the first report of human trials of photocyanine, and the results suggested that patients receive 180 J/cm illumination about 20-30 min at serum concentrations of photocyanine between 1000 and 2500 ng/ml at least 10 h after administration.
光动力疗法（PDT）方案基于光敏剂剂量、光剂量和药物 - 光间隔。Ⅰ期研究的目的是利用药代动力学（PK）和药效学（PD）为使用光氰宁的PDT选择最佳剂量和药物 - 光间隔。
招募了28名癌症患者。在试验A中，12名患者在180 - 270 J/cm光照前24小时静脉注射四种递增剂量之一的光氰宁。在试验B中，10名患者在120 J/cm光照前12 - 48小时输注0.2 mg/kg剂量。在试验C中，6名患者在180 - 270 J/cm光照前6或12小时输注0.1 mg/kg剂量。测量光氰宁的血清浓度，并进行模拟以评估组织中药物暴露对反应的影响。
对患者光氰宁水平的分析表明，二室模型最适合数据。模拟显示，注射后8 - 12小时药物进入组织和离开组织的速率相等。患者经历的疼痛与光氰宁血清水平有关，尤其是血清水平高于2500 ng/ml时。给药后至少12小时光照，血清水平高于1000 ng/ml时观察到的无反应者较少。
这是光氰宁人体试验的首次报告，结果表明患者在给药至少10小时后，光氰宁血清浓度在1000至2500 ng/ml之间时接受180 J/cm光照约20 - 30分钟。
