Mayo Clinic, Rochester, Minnesota 55905, USA.
Mol Ther. 2012 Oct;20(10):1998-2003. doi: 10.1038/mt.2012.146. Epub 2012 Aug 7.
Reovirus, a replication competent RNA virus, has preclinical activity against melanoma lines and xenografts. We conducted a phase II trial of reovirus in metastatic melanoma patients. Patients received 3 × 10(10) TCID50 on days 1-5 of each 28 day cycle, administered intravenously. Twenty-one eligible patients were enrolled. Treatment was well tolerated without any dose reductions having to be implemented. Post-treatment biopsy samples were obtained in 15 patients, 13/15 contained adequate tumor for correlative analysis. In two patients, productive reoviral replication (viral antigen coexpression with tubulin) was demonstrated, despite increase in neutralizing antibody titers. There were no objective responses although 75-90% tumor necrosis, consistent with treatment effect, was observed in one patient who had metastatic lesions surgically removed. Median time to progression and survival were 45 days (range 13-96 days) and 165 days (range 15 days-15.8 months) respectively. In conclusion, reovirus treatment was well tolerated in metastatic melanoma patients; viral replication was demonstrated in biopsy samples. Based on preclinical data showing synergy with taxane and platinum compounds, a phase II combination trial in metastatic melanoma patients is ongoing.
呼肠孤病毒是一种有复制能力的 RNA 病毒，在黑色素瘤细胞系和异种移植物中具有临床前活性。我们在转移性黑色素瘤患者中进行了呼肠孤病毒的 II 期试验。患者在每个 28 天周期的 1-5 天接受 3×10(10)TCID50 的静脉内给药。共纳入了 21 名符合条件的患者。治疗耐受性良好，无需减少剂量。在 15 名患者中获得了治疗后活检样本，15/15 样本中含有足够的肿瘤用于相关性分析。在两名患者中，尽管中和抗体滴度增加，但仍显示出有效的呼肠孤病毒复制（病毒抗原与微管蛋白共表达）。尽管有一名患者的转移性病变经手术切除后观察到 75-90%的肿瘤坏死，与治疗效果一致，但没有观察到客观反应。中位无进展生存期和总生存期分别为 45 天（范围 13-96 天）和 165 天（范围 15 天-15.8 个月）。总之，呼肠孤病毒治疗在转移性黑色素瘤患者中耐受性良好；在活检样本中证明了病毒复制。基于临床前数据显示与紫杉烷和铂类化合物具有协同作用，正在转移性黑色素瘤患者中进行 II 期联合试验。
