Freeman Arnold I, Zakay-Rones Zichria, Gomori John M, Linetsky Eduard, Rasooly Linda, Greenbaum Evgeniya, Rozenman-Yair Shira, Panet Amos, Libson Eugene, Irving Charles S, Galun Eithan, Siegal Tali
Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem 91120, Israel.
Mol Ther. 2006 Jan;13(1):221-8. doi: 10.1016/j.ymthe.2005.08.016. Epub 2005 Oct 28.
We undertook a Phase I/II trial in patients with apparent recurrent glioblastoma multiforme (GBM) based on imaging studies to determine the safety and tumor response of repetitive intravenous administration of NDV-HUJ, the oncolytic HUJ strain of Newcastle disease virus. The first part of the study utilized an accelerated intrapatient dose-escalation protocol with one-cycle dosage steps of 0.1, 0.32, 0.93, 5.9, and 11 billion infectious units (BIU) of NDV-HUJ (1 BIU = 1 x 10(9) EID(50) 50% egg infectious dose) followed by three cycles of 55 BIU. Virus was administered by intravenous infusion over 15 min. In the second part, patients received three cycles of 11 BIU. All patients without progressive disease were maintained with two doses of 11 BIU iv weekly. Eleven of the 14 enrolled patients (11-58 years, Karnofsky performance scale 50-90%) received treatment. Toxicity was minimal with Grade I/II constitutional fever being seen in 5 patients. Maximum tolerated dose was not achieved. Anti-NDV hemagglutinin antibodies appeared within 5-29 days. NDV-HUJ was recovered from blood, saliva, and urine samples and one tumor biopsy. One patient achieved a complete response. Intravenous NDV-HUJ is well tolerated. The findings of good tolerability and encouraging responses warrant the continued evaluation of NDV-HUJ in GBM, as well as other cancers.
基于影像学研究，我们对多形性胶质母细胞瘤（GBM）明显复发的患者进行了一项I/II期试验，以确定重复静脉注射新城疫病毒溶瘤HUJ株（NDV-HUJ）的安全性和肿瘤反应。研究的第一部分采用了加速的患者内剂量递增方案，NDV-HUJ的单周期剂量步骤为0.1、0.32、0.93、5.9和110亿感染单位（BIU）（1 BIU = 1 x 10(9) EID(50) 50%鸡胚感染剂量），随后是三个周期的55 BIU。病毒通过静脉输注15分钟给药。在第二部分中，患者接受三个周期的11 BIU。所有无疾病进展的患者每周静脉注射两剂11 BIU进行维持治疗。14名入组患者中的11名（年龄11 - 58岁，卡诺夫斯基功能状态评分50 - 90%）接受了治疗。毒性极小，5名患者出现I/II级全身性发热。未达到最大耐受剂量。抗NDV血凝素抗体在5 - 29天内出现。从血液、唾液、尿液样本和一次肿瘤活检中回收了NDV-HUJ。一名患者实现了完全缓解。静脉注射NDV-HUJ耐受性良好。良好耐受性和令人鼓舞的反应结果值得在GBM以及其他癌症中继续评估NDV-HUJ。
