REO-10: A Phase I Study of Intravenous Reovirus and Docetaxel in Patients with Advanced Cancer
REO-10: A Phase I Study of Intravenous Reovirus and Docetaxel in Patients with Advanced Cancer
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DOI：
10.1158/1078-0432.ccr-10-1233
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发表时间：
2010-11-15
影响因子：
11.5
通讯作者：
Pandha, Hardev S.
中科院分区：
文献类型：
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作者：
Comins, Charles;Spicer, James;Pandha, Hardev S.
目的：REOLYSIN（Oncolytics Biotech）由野生型溶瘤呼肠孤病毒组成，其对肿瘤细胞具有选择性细胞毒性，同时保留正常细胞。在一项I期研究中，作为单一药物，重复输注呼肠孤病毒是安全的，有抗肿瘤活性的证据。临床前研究表明呼肠孤病毒和化疗药物之间的协同作用的潜力。一项多中心、I期剂量递增研究旨在评估呼肠孤病毒联合多西他赛化疗治疗晚期癌症患者的安全性。实验设计：患者接受75 mg/m2多西他赛（第1天）和递增剂量的呼肠孤病毒，直至3 × 10（10）TCID 50结果：25例患者入组，24例患者接受治疗，其中23例完成至少一个周期，16例适合进行反应评估。在1例患者中观察到4级中性粒细胞减少的剂量限制性毒性，但未达到最大耐受剂量。在1例完全缓解和3例部分缓解中观察到抗肿瘤活性。观察到疾病控制率（完全缓解、部分缓解和疾病稳定合并）为88%。在三名患者的治疗后肿瘤活检中观察到呼肠孤病毒蛋白表达的免疫组织化学分析。呼肠孤病毒和多西他赛联合用药是安全的，有客观疾病缓解的证据，需要在多西他赛推荐给药方案的II期研究中进行进一步评价（75 mg/m2，每周三次）和呼肠孤病毒（3 x 10（10）TCID 50，第1-5天，每3周一次）。临床癌症研究; 16（22）; 5564-72。(C)2010年AACR。
Purpose: REOLYSIN (Oncolytics Biotech) consists of a wild-type oncolytic reovirus, which has selective cytotoxicity for tumor cells while sparing normal cells. In a phase I study as a single agent, repeated infusions of reovirus were safe with evidence of antitumor activity. Preclinical studies indicate potential for synergy between reovirus and chemotherapeutic agents. A multicenter, phase I dose escalation study was designed to assess the safety of combining reovirus with docetaxel chemotherapy in patients with advanced cancer.Experimental Design: Patients received 75 mg/m(2) docetaxel ( day 1) and escalating doses of reovirus up to 3 x 10(10) TCID50 (days 1-5) every 3 weeks.Results: Twenty-five patients were enrolled, and 24 patients were exposed to treatment, with 23 completing at least one cycle and 16 suitable for response assessment. Dose-limiting toxicity of grade 4 neutropenia was seen in one patient, but the maximum tolerated dose was not reached. Antitumor activity was seen with one complete response and three partial responses. A disease control rate (combined complete response, partial response, and stable disease) of 88% was observed. Immunohistochemical analysis of reovirus protein expression was observed in posttreatment tumor biopsies from three patients.Conclusion: The combination of reovirus and docetaxel is safe, with evidence of objective disease response, and warrants further evaluation in a phase II study at a recommended schedule of docetaxel (75 mg/m(2), three times weekly) and reovirus (3 x 10(10) TCID50, days 1-5, every 3 weeks). Clin Cancer Res; 16(22); 5564-72. (C) 2010 AACR.