A phase I study of intravenous oncolytic reovirus type 3 dearing in patients with advanced cancer

Laura Vidal, Hardev S. Pandha, Timothy A. Yap, Christine L. White, Katie Twigger, Richard Geoffrey Vile, Alan Melcher, Matt Coffey, Kevin J. Harrington, Johann S. DeBono

Research output: Contribution to journalArticle

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Abstract

Purpose: To determine the safety and feasibility of daily i.v. administration of wild-type oncolytic reovirus (type 3 Dearing) to patients with advanced cancer, assess viral excretion kinetics and antiviral immune responses, identify tumor localization and replication, and describe antitumor activity. Experimental Design: Patients received escalating doses of reovirus up to 3 × 1010 TCID50 for 5 consecutive days every 4 weeks. Viral excretion was assessed by reverse transcription-PCR and antibody response by cytotoxicity neutralization assay. Pretreatment and post-treatment tumor biopsies were obtained to measure viral uptake and replication. Results: Thirty-three patients received 76 courses of reovirus from 1 × 10 8 for 1 day up to 3 × 1010 TCID50 for 5 days, repeated every four weeks. Dose-limiting toxicity was not seen. Common grade1 to 2 toxicities included fever, fatigue, and headache, which were dose and cycle independent. Viral excretion at day 15 was not detected by reverse transcription-PCR at 25 cycles and only in 5 patients at 35 cycles. Neutralizing antibodies were detected in all patients and peaked at 4 weeks. Viral localization and replication in tumor biopsies were confirmed in 3 patients. Antitumor activity was seen by radiologic and tumor marker (carcinoembryonic antigen, CA19.9, and prostate-specific antigen) evaluation. Conclusions: Oncolytic reovirus can be safely and repeatedly administered by i.v. injection at doses up to 3 × 1010 TCID50 for 5 days every 4 weeks without evidence of severe toxicities. Productive reoviral infection of metastatic tumor deposits was confirmed. Reovirus is a safe agent that warrants further evaluation in phase II studies.

Original languageEnglish (US)
Pages (from-to)7127-7137
Number of pages11
JournalClinical Cancer Research
Volume14
Issue number21
DOIs
StatePublished - Nov 1 2008

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Mammalian orthoreovirus 3
Neoplasms
Reverse Transcription
Mammalian Orthoreovirus
Biopsy
Polymerase Chain Reaction
Carcinoembryonic Antigen
Differentiation Antigens
Neoplasm Antigens
Prostate-Specific Antigen
Tumor Biomarkers
Neutralizing Antibodies
Antibody Formation
Antiviral Agents
Fatigue
Headache
Research Design
Fever
Safety
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A phase I study of intravenous oncolytic reovirus type 3 dearing in patients with advanced cancer. / Vidal, Laura; Pandha, Hardev S.; Yap, Timothy A.; White, Christine L.; Twigger, Katie; Vile, Richard Geoffrey; Melcher, Alan; Coffey, Matt; Harrington, Kevin J.; DeBono, Johann S.

In: Clinical Cancer Research, Vol. 14, No. 21, 01.11.2008, p. 7127-7137.

Research output: Contribution to journalArticle

Vidal, L, Pandha, HS, Yap, TA, White, CL, Twigger, K, Vile, RG, Melcher, A, Coffey, M, Harrington, KJ & DeBono, JS 2008, 'A phase I study of intravenous oncolytic reovirus type 3 dearing in patients with advanced cancer', Clinical Cancer Research, vol. 14, no. 21, pp. 7127-7137. https://doi.org/10.1158/1078-0432.CCR-08-0524
Vidal, Laura ; Pandha, Hardev S. ; Yap, Timothy A. ; White, Christine L. ; Twigger, Katie ; Vile, Richard Geoffrey ; Melcher, Alan ; Coffey, Matt ; Harrington, Kevin J. ; DeBono, Johann S. / A phase I study of intravenous oncolytic reovirus type 3 dearing in patients with advanced cancer. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 21. pp. 7127-7137.
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AU - Vile, Richard Geoffrey

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