Two-stage phase I dose-escalation study of intratumoral reovirus type 3 dearing and palliative radiotherapy in patients with advanced cancers

Kevin J. Harrington, Eleni M. Karapanagiotou, Victoria Roulstone, Katie R. Twigger, Christine L. White, Laura Vidal, Debbie Beirne, Robin Prestwich, Kate Newbold, Merina Ahmed, Khin Thway, Christopher M. Nutting, Matt Coffey, Dean Harris, Richard G. Vile, Hardev S. Pandha, Johann S. DeBono, Alan A. Melcher

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Purpose: To determine the safety and feasibility of combining intratumoral reovirus and radiotherapy in patients with advanced cancer and to assess viral biodistribution, reoviral replication in tumors, and antiviral immune responses. Experimental Design: Patients with measurable disease amenable to palliative radiotherapy were enrolled. In the first stage, patients received radiotherapy (20 Gy in five fractions) plus two intratumoral injections of RT3D at doses between 1 x 108 and 1 x 1010 TCID50. In the second stage, the radiotherapy dose was increased (36 Gy in 12 fractions) and patients received two, four, or six doses of RT3D at 1 x 1010 TCID50. End points were safety, viral replication, immunogenicity, and antitumoral activity. Results: Twenty-three patients with various solid tumors were treated. Dose-limiting toxicity was not seen. The most common toxicities were grade 2 (or lower) pyrexia, influenza-like symptoms, vomiting, asymptomatic lymphopenia, and neutropenia. There was no exacerbation of the acute radiation reaction. Reverse transcription-PCR (RT-PCR) studies of blood, urine, stool, and sputum were negative for viral shedding. In the low-dose (20 Gy in five fractions) radiation group, two of seven evaluable patients had a partial response and five had stable disease. In the high-dose (36 Gy in 12 fractions) radiation group, five of seven evaluable patients had partial response and two stable disease. Conclusions: The combination of intratumoral RT3D and radiotherapy was well tolerated. The favorable toxicity profile and lack of vector shedding means that this combination should be evaluated in newly diagnosed patients receiving radiotherapy with curative intent.

Original languageEnglish (US)
Pages (from-to)3067-3077
Number of pages11
JournalClinical Cancer Research
Volume16
Issue number11
DOIs
StatePublished - Jun 1 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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