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Abstract

Purpose: 

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.

Experimental Design:

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.

Results: 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.

Conclusions: 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.

Author information​

Mell LK1, Brumund KT2, Daniels GA3, Advani SJ4, Zakeri K4, Wright ME4, Onyeama SJ4, Weisman RA2, Sanghvi PR4, Martin PJ5, Szalay AA4.

1 Center for Translational Radiation Medicine and Imaging, Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California. lmell@ucsd.edu.

2 Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of California San Diego, La Jolla, California.

3 Center for Personalized Cancer Therapy, and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, California.

4 Center for Translational Radiation Medicine and Imaging, Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.

5 Department of Otolaryngology, Kaiser Permanente, San Diego, California.