Coleman R L, Miller D S
Department of Obstetrics and Gynecology, University of Texas, Southwestern Medical Center, Dallas 75235, USA.
Semin Oncol. 1997 Dec;24(6 Suppl 20):S20-55-S20-63.
Topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a derivative of the topoisomerase I inhibitor camptothecin, was approved by the Food and Drug Administration in May 1996 for the salvage treatment of ovarian cancer. It has shown promising clinical activity in a variety of solid tumors, including cervical cancer. Phase II and III trials in patients with cisplatin-resistant ovarian cancer have been conducted using a regimen of a single 30-minute intravenous topotecan infusion (1.5 mg/m2/d) for 5 days, repeated every 21 days. Significant responses, both partial and complete, have been observed in 14% to 21% of patients, with stable disease achieved in as many as 61%. In advanced or recurrent cervical cancer, partial response or stable disease was achieved in 59% of phase II trial patients. Myelosuppression is the major dose-limiting toxicity associated with topotecan. In general, the severity of myelosuppression shows a positive correlation to the magnitude of exposure to topotecan. Support with granulocyte colony-stimulating factor may partially ameliorate myelosuppressive effects.
拓扑替康（希罗达；史克必成制药公司，宾夕法尼亚州费城）是拓扑异构酶I抑制剂喜树碱的衍生物，于1996年5月获美国食品药品监督管理局批准用于卵巢癌的挽救治疗。它在包括宫颈癌在内的多种实体瘤中显示出有前景的临床活性。针对顺铂耐药的卵巢癌患者进行了II期和III期试验，采用单次30分钟静脉输注拓扑替康（1.5mg/m²/天）共5天的方案，每21天重复一次。在14%至21%的患者中观察到了显著反应，包括部分缓解和完全缓解，多达61%的患者病情稳定。在晚期或复发性宫颈癌中，II期试验患者中有59%达到部分缓解或病情稳定。骨髓抑制是与拓扑替康相关的主要剂量限制性毒性。一般来说，骨髓抑制的严重程度与拓扑替康的暴露量呈正相关。使用粒细胞集落刺激因子支持可能部分改善骨髓抑制作用。
