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 Geoffrey Vile, Hardev S. Pandha, Johann S. DeBono, Alan A. Melcher

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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 10 8 and 1 x 10 10 TCID 50. 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 10 10 TCID 50. 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

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Mammalian orthoreovirus 3
Radiotherapy
Neoplasms
Radiation
Virus Shedding
Safety
Lymphopenia
Neutropenia
Sputum
Human Influenza
Reverse Transcription
Vomiting
Antiviral Agents
Research Design
Fever
Urine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Harrington, K. J., Karapanagiotou, E. M., Roulstone, V., Twigger, K. R., White, C. L., Vidal, L., ... Melcher, A. A. (2010). Two-stage phase I dose-escalation study of intratumoral reovirus type 3 dearing and palliative radiotherapy in patients with advanced cancers. Clinical Cancer Research, 16(11), 3067-3077. https://doi.org/10.1158/1078-0432.CCR-10-0054

Two-stage phase I dose-escalation study of intratumoral reovirus type 3 dearing and palliative radiotherapy in patients with advanced cancers. / Harrington, Kevin J.; Karapanagiotou, Eleni M.; Roulstone, Victoria; Twigger, Katie R.; White, Christine L.; Vidal, Laura; Beirne, Debbie; Prestwich, Robin; Newbold, Kate; Ahmed, Merina; Thway, Khin; Nutting, Christopher M.; Coffey, Matt; Harris, Dean; Vile, Richard Geoffrey; Pandha, Hardev S.; DeBono, Johann S.; Melcher, Alan A.

In: Clinical Cancer Research, Vol. 16, No. 11, 01.06.2010, p. 3067-3077.

Research output: Contribution to journalArticle

Harrington, KJ, Karapanagiotou, EM, Roulstone, V, Twigger, KR, White, CL, Vidal, L, Beirne, D, Prestwich, R, Newbold, K, Ahmed, M, Thway, K, Nutting, CM, Coffey, M, Harris, D, Vile, RG, Pandha, HS, DeBono, JS & Melcher, AA 2010, 'Two-stage phase I dose-escalation study of intratumoral reovirus type 3 dearing and palliative radiotherapy in patients with advanced cancers', Clinical Cancer Research, vol. 16, no. 11, pp. 3067-3077. https://doi.org/10.1158/1078-0432.CCR-10-0054
Harrington, Kevin J. ; Karapanagiotou, Eleni M. ; Roulstone, Victoria ; Twigger, Katie R. ; White, Christine L. ; Vidal, Laura ; Beirne, Debbie ; Prestwich, Robin ; Newbold, Kate ; Ahmed, Merina ; Thway, Khin ; Nutting, Christopher M. ; Coffey, Matt ; Harris, Dean ; Vile, Richard Geoffrey ; Pandha, Hardev S. ; DeBono, Johann S. ; Melcher, Alan A. / Two-stage phase I dose-escalation study of intratumoral reovirus type 3 dearing and palliative radiotherapy in patients with advanced cancers. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 11. pp. 3067-3077.
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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 10 8 and 1 x 10 10 TCID 50. 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 10 10 TCID 50. 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.",
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T1 - Two-stage phase I dose-escalation study of intratumoral reovirus type 3 dearing and palliative radiotherapy in patients with advanced cancers

AU - Harrington, Kevin J.

AU - Karapanagiotou, Eleni M.

AU - Roulstone, Victoria

AU - Twigger, Katie R.

AU - White, Christine L.

AU - Vidal, Laura

AU - Beirne, Debbie

AU - Prestwich, Robin

AU - Newbold, Kate

AU - Ahmed, Merina

AU - Thway, Khin

AU - Nutting, Christopher M.

AU - Coffey, Matt

AU - Harris, Dean

AU - Vile, Richard Geoffrey

AU - Pandha, Hardev S.

AU - DeBono, Johann S.

AU - Melcher, Alan A.

PY - 2010/6/1

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N2 - 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 10 8 and 1 x 10 10 TCID 50. 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 10 10 TCID 50. 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.

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