Forsyth Peter, Roldán Gloria, George David, Wallace Carla, Palmer Cheryl Ann, Morris Don, Cairncross Gregory, Matthews Maureen Vallee, Markert James, Gillespie Yancey, Coffey Matt, Thompson Brad, Hamilton Mark
Department of Oncology, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Mol Ther. 2008 Mar;16(3):627-32. doi: 10.1038/sj.mt.6300403. Epub 2008 Feb 5.
Reovirus is an oncolytic virus with activity in in vivo models of malignant gliomas (MGs). The primary aims were to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of intratumoral administration of reovirus in patients with recurrent MGs. Response, survival, and time to progression (TTP) were secondary aims. Patients were adults, had Karnofsky Performance score > or = 60, received prior radiotherapy with or without chemotherapy, and had up to the third recurrence of MG. Reovirus was administered intratumorally stereotactically at 1 x 10(7), 1 x 10(8), or 1 x 10(9) tissue culture infectious dose 50 (TCID50) in a volume of 0.9 ml. Twelve patients were treated at three dose levels (3, 6, and 3 patients, respectively). Seven were men, median Karnofsky Performance score was 80, and median age was 53.5 years. There were no grade III or IV adverse events (AEs) definitely or probably related to treatment. Ten patients had tumor progression, one had stabilization, and one was not evaluable for response. Median survival was 21 weeks (range, 6-234), and one is alive 54 months after treatment. Median TTP was 4.3 weeks (range, 2.6-39). An MTD was not reached. The intratumoral administration of the genetically unmodified reovirus was well tolerated using these doses and schedule, in patients with recurrent MG.
呼肠孤病毒是一种在恶性胶质瘤（MG）体内模型中具有活性的溶瘤病毒。主要目的是确定呼肠孤病毒瘤内给药在复发性MG患者中的剂量限制性毒性（DLT）和最大耐受剂量（MTD）。反应、生存和疾病进展时间（TTP）是次要目的。患者为成年人，卡氏评分≥60，接受过或未接受过化疗的先前放疗，且MG复发最多达三次。呼肠孤病毒以1×10⁷、1×10⁸或1×10⁹组织培养感染剂量50（TCID50）的剂量，在0.9毫升体积内通过立体定向瘤内给药。在三个剂量水平分别治疗了12名患者（分别为3名、6名和3名患者）。7名男性，卡氏评分中位数为80，年龄中位数为53.5岁。没有明确或可能与治疗相关的III级或IV级不良事件（AE）。10名患者肿瘤进展，1名病情稳定，1名无法评估反应。中位生存期为21周（范围6 - 234周），1名患者在治疗后54个月仍存活。中位TTP为4.3周（范围2.6 - 39周）。未达到MTD。在复发性MG患者中，使用这些剂量和给药方案，基因未修饰的呼肠孤病毒瘤内给药耐受性良好。
