Kane Robert C, McGuinn W David, Dagher Ramzi, Justice Robert, Pazdur Richard
Office of Oncology Drug Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Bldg. 22, Room 2109, Silver Spring, Maryland 20993-0002, USA.
Oncologist. 2008 Apr;13(4):445-50. doi: 10.1634/theoncologist.2007-0247.
Management of anthracycline extravasation is problematic and most reports are anecdotal. On September 6, 2007, the U.S. Food and Drug Administration approved Totect 500 mg (dexrazoxane hydrochloride for injection) for the treatment of extravasation resulting from i.v. anthracycline chemotherapy. In two studies, a total of 57 evaluable patients experienced extravasation from peripheral vein or central venous access sites with local swelling, pain, or redness. The presence of anthracycline in skin biopsy tissue was confirmed by tissue fluorescence, and treatment with a 3-day schedule of dexrazoxane began within 6 hours of the event. The primary endpoint was a reduction in the need for surgical intervention. Only one patient required surgical repair of the injury site, and late sequelae in the remainder were absent or mild. Also, the sponsor, TopoTarget A/S, Copenhagen, Denmark, performed controlled nonclinical studies in support of dexrazoxane dose and timing for the reduction of tissue injury resulting from anthracycline extravasation. For this uncommon but serious complication of anthracycline therapy, the need for surgical intervention was 1.7% with this regimen.
蒽环类药物外渗的处理存在问题，且大多数报告都是轶事性的。2007年9月6日，美国食品药品监督管理局批准了500毫克的Totect（注射用盐酸右丙亚胺）用于治疗静脉注射蒽环类化疗药物引起的外渗。在两项研究中，共有57例可评估患者出现外周静脉或中心静脉置管部位的外渗，伴有局部肿胀、疼痛或发红。通过组织荧光证实皮肤活检组织中存在蒽环类药物，并在事件发生后6小时内开始为期3天的右丙亚胺治疗。主要终点是减少手术干预的需求。只有1例患者需要对损伤部位进行手术修复，其余患者无晚期后遗症或后遗症较轻。此外，申办方丹麦哥本哈根的TopoTarget A/S公司进行了对照非临床研究，以支持右丙亚胺的剂量和给药时间，用于减少蒽环类药物外渗导致的组织损伤。对于这种蒽环类治疗罕见但严重的并发症，该治疗方案的手术干预需求为1.7%。
