Su Li1,2, Bingtian Bi1,2, Guangyu Luo1,3, Jing Zhan1,2, Rong Zhang1,3, Jibin Li1,2, Naisheng Chen4, Jinling Huang4, Jinping Xue5, Guoliang Xu6,7. 1. 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. 2. Department of Clinical Trial Center, Cancer Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China. 3. Department of Endoscopy, Cancer Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China. 4. College of Chemistry, Fuzhou University, Fuzhou, 350108, People's Republic of China. 5. College of Chemistry, Fuzhou University, Fuzhou, 350108, People's Republic of China. xuejinping66@fzu.edu.cn. 6. 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. xugl@sysucc.org.cn. 7. Department of Endoscopy, Cancer Center, Sun Yat-Sen University, Guangzhou, 510060, People's Republic of China. xugl@sysucc.org.cn.
Abstract
PURPOSE: 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). METHODS: 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/cm2 illumination. 0.2 mg/kg dose was infused to ten patients 12-48 h prior to 120 J/cm2 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/cm2 illumination. Serum concentrations of photocyanine were measured, and simulations were performed to assess the effect of drug exposure in tissue on responses. RESULTS: 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. CONCLUSION: It is the first report of human trials of photocyanine, and the results suggested that patients receive 180 J/cm2 illumination about 20-30 min at serum concentrations of photocyanine between 1000 and 2500 ng/ml at least 10 h after administration.
PURPOSE: 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). METHODS: Twenty-eight cancerpatients were enrolled. In trial A, 12 patients received one of four ascending doses of photocyanine intravenously 24 h prior to 180-270 J/cm2 illumination. 0.2 mg/kg dose was infused to ten patients 12-48 h prior to 120 J/cm2 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/cm2 illumination. Serum concentrations of photocyanine were measured, and simulations were performed to assess the effect of drug exposure in tissue on responses. RESULTS: 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. CONCLUSION: It is the first report of human trials of photocyanine, and the results suggested that patients receive 180 J/cm2 illumination about 20-30 min at serum concentrations of photocyanine between 1000 and 2500 ng/ml at least 10 h after administration.