Phase II Trial of Intravenous Administration of Reolysin® (Reovirus Serotype-3-dearing Strain) in Patients with Metastatic Melanoma
Phase II Trial of Intravenous Administration of Reolysin® (Reovirus Serotype-3-dearing Strain) in Patients with Metastatic Melanoma
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DOI：
10.1038/mt.2012.146
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发表时间：
2012-10-01
影响因子：
12.4
通讯作者：
Kendra, Kari
中科院分区：
文献类型：
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作者：
Galanis, Evanthia;Markovic, Svetomir N.;Kendra, Kari
呼肠孤病毒是一种具有复制能力的RNA病毒，对黑色素瘤系和异种移植物具有临床前活性。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28天周期的第1-5天静脉给予3 × 10(10) TCID50。21名符合条件的患者入组。治疗耐受性良好，无需减少剂量。15例患者获得治疗后活检样本，其中13/15包含足够的肿瘤进行相关性分析。在两名患者中，尽管中和抗体滴度增加，但仍证明了呼肠孤病毒的增殖（病毒抗原与微管蛋白共表达）。尽管在一例手术切除转移灶的患者中观察到75-90%的肿瘤坏死，但没有客观反应，这与治疗效果一致。中位进展时间和生存期分别为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；在活检样本中证实了病毒复制。基于临床前数据显示与紫杉烷和铂化合物的协同作用，转移性黑色素瘤患者的II期联合试验正在进行中。
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 x 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.