Center for Translational Radiation Medicine and Imaging, Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.
Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California.
Clin Cancer Res. 2017 Oct 1;23(19):5696-5702. doi: 10.1158/1078-0432.CCR-16-3232. Epub 2017 Jul 5.
Preclinical models have shown that the effectiveness of GL-ONC1, a modified oncolytic vaccinia virus, is enhanced by radiation and chemotherapy. The purpose of this study was to determine the safety of GL-ONC1 when delivered intravenously with chemoradiotherapy to patients with primary, nonmetastatic head and neck cancer. Patients with locoregionally advanced unresected, nonmetastatic carcinoma of the head/neck, excluding stage III-IVA p16-positive oropharyngeal cancers, were treated with escalating doses and cycles of intravenous GL-ONC1, along with radiotherapy and chemotherapy. The primary aims were to define the MTD and dose-limiting toxicities, and to recommend a dose for phase II trials. Between May 2012 and December 2014, 19 patients were enrolled. The most frequent adverse reactions included grade 1-2 rigors, fever, fatigue, and rash. Grade 3 adverse reactions included hypotension, mucositis, nausea, and vomiting. In 2 patients, the rash was confirmed as viral in origin by fluorescence imaging and viral plaque assay. In 4 patients, viral presence in tumor was confirmed on midtreatment biopsy by quantitative PCR. In 1 patient, live virus was confirmed in a tongue tumor 7 days after receiving the first dose of virus. The MTD was not reached. With median follow-up of 30 months, 1-year (2-year) progression-free survival and overall survival were 74.4% (64.1%) and 84.6% (69.2%), respectively. Delivery of GL-ONC1 is safe and feasible in patients with locoregionally advanced head/neck cancer undergoing standard chemoradiotherapy. A phase II study is warranted to further investigate this novel treatment strategy. .
临床前模型表明，经修饰的溶瘤痘苗病毒 GL-ONC1 的有效性可通过放射治疗和化学疗法增强。本研究的目的是确定 GL-ONC1 在与化学放射疗法联合用于局部晚期未切除的非转移性头颈部癌症患者时的安全性。对局部晚期未切除的非转移性头/颈癌患者（不包括 III-IVA 期 p16 阳性口咽癌）进行静脉内 GL-ONC1 递增剂量和周期治疗，同时进行放射治疗和化学治疗。主要目的是确定最大耐受剂量和剂量限制性毒性，并推荐用于 II 期试验的剂量。2012 年 5 月至 2014 年 12 月，共纳入 19 例患者。最常见的不良反应包括 1-2 级寒战、发热、乏力和皮疹。3 级不良反应包括低血压、黏膜炎、恶心和呕吐。在 2 例患者中，皮疹经荧光成像和病毒斑试验证实为病毒起源。在 4 例患者中，通过中期治疗活检确认肿瘤中存在病毒，采用定量 PCR。在 1 例患者中，在接受第 1 剂病毒后 7 天，舌肿瘤中证实存在活病毒。未达到最大耐受剂量。中位随访 30 个月后，1 年（2 年）无进展生存率和总生存率分别为 74.4%（64.1%）和 84.6%（69.2%）。在接受标准化学放射治疗的局部晚期头/颈癌患者中，GL-ONC1 的递送是安全且可行的。需要进行 II 期研究以进一步探讨这种新的治疗策略。
