Mahalingam Devalingam, Fountzilas Christos, Moseley Jennifer, Noronha Nicole, Tran Hue, Chakrabarty Romit, Selvaggi Giovanni, Coffey Matthew, Thompson Brad, Sarantopoulos John
Division of Hematology/Oncology, Cancer Therapy and Research Center, University of Texas Health Science Center, 7979 Wurzbach Rd, San Antonio, TX, 78229, USA.
Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
Cancer Chemother Pharmacol. 2017 Apr;79(4):697-703. doi: 10.1007/s00280-017-3260-6. Epub 2017 Mar 13.
REOLYSIN (pelareorep) is an investigational new drug, consisting of a live, replication-competent, Reovirus Type 3 Dearing strain in a proprietary formulation. Several preclinical and clinical trials with REOLYSIN on a wide range of cancer indications have demonstrated antineoplastic activity on cells with activated RAS-signaling pathway. Furthermore, long-term survival benefits were evident in post-treatment patients indicating a potential antitumor immune response triggered by REOLYSIN. Numerous mono and/or combination therapy studies with the agent showed a consistent safety profile. The current study is a phase II, single-arm, open label trial of REOLYSIN in combination with carboplatin and paclitaxel for patients with advanced melanoma. Results from the 14 patients enrolled in the study exhibited no grade 4 adverse events or deaths but manageable grade-3 toxicities commonly attributed to REOLYSIN, including pyrexia, chills, myalgia, pain, fatigue, and nausea. The number of treatment cycles ranged from 2 to 20 with a median of 6 cycles. The study met its treatment and efficacy goal for the first stage with three partial responses (ORR was 21%). No complete responses were noted. The median PFS and OS were 5.2 and 10.9 months, respectively. The 1-year OS was 43% with a disease control rate of 85%. In conclusion, REOLYSIN combined with carboplatin and paclitaxel is a safe and potentially efficacious therapy for patients with advanced malignant melanoma. Additional combination studies using REOLYSIN with chemo/immunotherapy drugs may support more favorable outcomes for patients in this indication.
瑞欧力辛（pelareorep）是一种研究性新药，由一种具有复制能力的活的3型迪尔林呼肠孤病毒株（Reovirus Type 3 Dearing strain）制成的专利配方。多项关于瑞欧力辛针对多种癌症适应症的临床前和临床试验已证明其对具有激活RAS信号通路的细胞具有抗肿瘤活性。此外，治疗后的患者有明显的长期生存获益，表明瑞欧力辛触发了潜在的抗肿瘤免疫反应。该药物的众多单药和/或联合治疗研究显示出一致的安全性。本研究是一项II期单臂开放标签试验，评估瑞欧力辛联合卡铂和紫杉醇用于晚期黑色素瘤患者的疗效。该研究纳入的14例患者未出现4级不良事件或死亡，但出现了通常归因于瑞欧力辛的可控3级毒性，包括发热、寒战、肌痛、疼痛、疲劳和恶心。治疗周期数为2至20个，中位数为6个周期。该研究在第一阶段达到了治疗和疗效目标，有3例部分缓解（客观缓解率为21%）。未观察到完全缓解。无进展生存期和总生存期的中位数分别为5.2个月和10.9个月。1年总生存率为43%，疾病控制率为85%。总之，瑞欧力辛联合卡铂和紫杉醇对晚期恶性黑色素瘤患者是一种安全且可能有效的治疗方法。使用瑞欧力辛与化疗/免疫治疗药物的更多联合研究可能会为该适应症的患者带来更有利的结果。
