Rosenthal D I, Becerra C R, Toto R D, Carbone D P, Frenkel E P
Department of Radiation Oncology, University of Pennsylvania Medical Center, Philadelphia 19104-4283, USA.
Am J Clin Oncol. 2000 Dec;23(6):593-8. doi: 10.1097/00000421-200012000-00013.
Gadolinium (III) texaphyrin (Gd-Tex) (NSC 695238) is a potential radiation sensitizer that selectively localizes in tumors and is detectable by magnetic resonance imaging (MRI). In this single-dose phase I trial, reversible renal injury was the dose-limiting toxicity. This report details that renal injury. A single intravenous dose of Gd-Tex was followed 2 hours later by radiation therapy. The Gd-Tex dose was escalated in 13 patient cohorts. Doses ranged from 0.6 to 29.6 mg/kg. The maximum tolerated dosage (MTD) was 22.3 mg/kg. Three patients had grade II and one had grade III acute nonoliguric renal failure at the 22.3 and 29.6 mg/kg dose levels. The injury was always transient, and responded to fluid restriction and renal diet. In all patients, transient green discoloration including urine developed at doses > or =7.1 mg/kg. MRI studies demonstrated image enhancement in the liver, kidneys, and in primary and metastatic tumors in all patients receiving >5.4 mg/kg. It is important that the liver and kidneys be excluded from the radiation volume. Gd-Tex was well tolerated at doses below the MTD. It is important that the liver and kidneys be excluded from the radiation volume. We recommend that 16.7 mg/kg be used as the maximum single dose to obviate even low grade renal toxicity.
钆（III） texaphyrin（Gd-Tex）（NSC 695238）是一种潜在的辐射增敏剂，可选择性地定位于肿瘤中，并可通过磁共振成像（MRI）检测到。在这项单剂量I期试验中，可逆性肾损伤是剂量限制性毒性。本报告详细描述了这种肾损伤情况。静脉注射单剂量的Gd-Tex后2小时进行放射治疗。在13个患者队列中逐步增加Gd-Tex剂量。剂量范围为0.6至29.6mg/kg。最大耐受剂量（MTD）为22.3mg/kg。在22.3和29.6mg/kg剂量水平下，3例患者出现II级急性非少尿性肾衰竭，1例出现III级急性非少尿性肾衰竭。损伤总是短暂的，通过限制液体摄入和肾脏饮食可缓解。所有剂量≥7.1mg/kg的患者均出现包括尿液在内的短暂绿色变色。MRI研究表明，所有接受>5.4mg/kg剂量的患者肝脏、肾脏以及原发性和转移性肿瘤均有图像增强。将肝脏和肾脏排除在放射野之外很重要。在低于MTD的剂量下，Gd-Tex耐受性良好。将肝脏和肾脏排除在放射野之外很重要。我们建议将16.7mg/kg用作最大单剂量，以避免即使是低级别肾毒性的发生。
