A Phase I trial using local regional treatment, nonlethal irradiation, intratumoral and systemic polyinosinic-polycytidylic acid polylysine carboxymethylcellulose to treat liver cancer: in search of the abscopal effect
Authors de la Torre AN, Contractor S, Castaneda I, Cathcart CS, Razdan D, Klyde D, Kisza P, Gonzales SF, Salazar AM
Received 10 March 2017
Accepted for publication 16 June 2017
Published 7 August 2017 Volume 2017:4 Pages 111—121
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Ahmed O. Kaseb
Andrew N de la Torre,1,2 Sohail Contractor,3 Ismael Castaneda,1 Charles S Cathcart,4 Dolly Razdan,5 David Klyde,3 Piotr Kisza,3 Sharon F Gonzales,3 Andres M Salazar6
1Department of Surgery, St Joseph’s Regional Medical Center, Paterson, 2Department of Surgery, Rutgers New Jersey Medical School-University Hospital, 3Department of Interventional Radiology, Rutgers New Jersey Medical School-University Hospital, 4Department of Radiation Oncology, Beth Israel Medical Center, Newark, 5Department of Radiation Oncology, Clara Maas Hospital, Belleville, NJ, 6Oncovir, Washington, DC, USA
Purpose: To determine the safety of an approach to immunologically enhance local treatment of hepatocellular cancer (HCC) by combining nonlethal radiation, local regional therapy with intratumoral injection, and systemic administration of a potent Toll-like receptor (TLR) immune adjuvant.
Methods: Patients with HCC not eligible for liver transplant or surgery were subject to: 1) 3 fractions of 2-Gy focal nonlethal radiation to increase tumor antigen expression, 2) intra-/peri-tumoral (IT) injection of the TLR3 agonist, polyinosinic-polycytidylic acid polylysine carboxymethylcellulose (poly-ICLC), to induce an immunologic “danger” response in the tumor microenvironment with local regional therapy, and 3) systemic boosting of immunity with intramuscular poly-ICLC. Primary end points were safety and tolerability; secondary end points were progression-free survival (PFS) and overall survival (OS) at 6 months, 1 year, and 2 years.
Results: Eighteen patients with HCC not eligible for surgery or liver transplant were treated. Aside from 1 embolization-related severe adverse event, all events were ≤grade II. PFS was 66% at 6 months, 39% at 12 months, and 28% at 24 months. Overall 1-year survival was 69%, and 2-year survival 38%. In patients <60 years old, 2-year survival was 62.5% vs. 11.1% in patients aged >60 years (P<0.05). Several patients had prolonged PFS and OS.
Conclusion: Intra-tumoral injection of the TLR3 agonist poly-ICLC in patients with HCC is safe and tolerable when combined with local nonlethal radiation and local regional treatment. Further work is in progress to evaluate if this approach improves survival compared to local regional treatment alone and characterize changes in anticancer immunity.
Keywords: immunotherapy, autologous vaccine, liver cancer, human trial, Toll-like receptor
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