Photofrin uptake in the tumor and normal tissues of patients receiving intraperitoneal photodynamic therapy
Photofrin uptake in the tumor and normal tissues of patients receiving intraperitoneal photodynamic therapy
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DOI：
10.1158/1078-0432.ccr-06-0953
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发表时间：
2006-09-15
影响因子：
11.5
通讯作者：
Busch, Theresa M.
中科院分区：
文献类型：
--
作者：
Hahn, Stephen M.;Putt, Mary E.;Busch, Theresa M.
目的：Photofrin 介导的 i.p. 的 II 期试验之前的报告显示光动力疗法的疗效有限，并且具有显着的急性毒性，但不是慢性毒性。该试验的次要目的和本报告的主题是确定肿瘤和正常组织中光敏素的摄取。实验设计：患者在减瘤手术前48小时接受光敏素2.5mg/kg肌肉注射。通过对从手术中切除的肿瘤和正常组织中提取的药物进行分光荧光分析来测量光敏素的摄取。使用混合效应模型对这些组织中药物摄取的差异进行统计学考虑。结果：对从参与试验的 100 名患者中的 58 名收集的 301 个样本中测量了光敏素浓度。在正常组织中，药物摄取随七种不同组织类型的变化而显着不同（P < 0.0001）。在肠道毒性限制组织中，全层大肠和小肠中基于模型的平均 (SE) A 水平分别为 2.70 ng/mg (0.32 ng/mg) 和 3.42 ng/mg (0.24 ng/mg)。在肿瘤中，药物摄取随患者队列的变化而显着不同（P = 0.0015）：卵巢癌、胃癌或小肠癌患者中基于模型的平均 Photofrin 水平为 3.32 至 5.31 ng/mg；肉瘤、阑尾癌或结肠癌患者为 2.09 至 2.45 ng/mg；假粘液瘤患者为 0.93 ng/mg。卵巢癌、胃癌和小肠癌的光敏素摄取量显着高于全层大肠和/或小肠。然而，肿瘤与肠道中平均药物水平的比率适中（
Purpose: A phase II trial of Photofrin-mediated i.p. photodynamic therapy shown in a previous report limited efficacy and significant acute, but not chronic, toxicity. A secondary aim of this trial and the subject of this report is to determine Photofrin uptake in tumor and normal tissues.Experimental Design: Patients received Photofrin, 2.5 mg/kg, im., 48 hours before debulking surgery. Photofrin uptake was measured by spectroflurometric analysis of drug extracted from tumor and normal tissues removed at surgery. Differences in drug uptake among these tissues were statistically considered using mixed-effects models.Results: Photofrin concentration was measured in 301 samples collected from 58 of 100 patients enrolled on the trial. In normal tissues, drug uptake significantly (P < 0.0001) differed as a function of seven different tissue types. In the toxicity-limiting tissue of intestine, the model-based mean (SE) A level was 2.70 ng/mg (0.32 ng/mg) and 3.42 ng/mg (0.24 ng/mg) in full-thickness Photo large and small intestine, respectively. In tumors, drug uptake significantly (P = 0.0015) differed as a function of patient cohort: model-based mean Photofrin level was 3.32 to 5.31 ng/mg among patients with ovarian, gastric, or small bowel cancer; 2.09 to 2.45 ng/mg among patients with sarcoma and appendiceal or colon cancer; and 0.93 ng/mg in patients with pseudomyxoma. Ovarian, gastric, and small bowel cancers showed significantly higher Photofrin uptake than full-thickness large and/or small intestine. However, the ratio of mean drug level in tumor versus intestine was modest (