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Title: The potential therapeutic gain of radiation-associated gene therapy with the suicide gene cytosine deaminase
Authors: Lambin, Philippe ×
Nuyts, Sandra
Landuyt, W
Theys, Jan
de Bruijn, Ernst
Anné, Jozef
Van Mellaert, Lieve
Fowler, J #
Issue Date: Mar-2000
Series Title: International journal of radiation biology vol:76 issue:3 pages:285-93
Abstract: PURPOSE: To estimate the concentration of 5-fluorocytosine (5-FC), necessary for conversion to 5-fluorouracil (5-FU) in tumours transduced with the gene cytosine deaminase (CD), to achieve clinically significant radiosensitization to radiotherapy. MATERIALS AND METHODS: Starting with a tumour control probability (TCP) of 37% from radiotherapy of 66 Gy in 2 Gy fractions, estimates were made of increase in TCP expected from sensitizer enhancement ratios (SER) of 1.1, 1.2, etc. SER values for 5-FU were obtained from a literature review. Clinical toxicity of 5-FC is also reviewed. RESULTS: 5-FU has been reported to be an effective radiosensitizer if maintained for several days after each irradiation at concentrations of 0.6-0.9 microg/ml in surrounding medium. 5-FC is well tolerated by patients at concentrations of 25-100 microg/ml (average 60 microg/ml) for 6 weeks in standard antifungal treatment. Sufficient 5-FU should be available if conversion efficiency from 5-FC is 1-3%. SER values of 1.1 to 1.2 should be achievable with daily 2 Gy fractions. In vitro and xenograft experiments are reviewed and they do not contradict the conclusions. CONCLUSIONS: Increases in tumour control of 20 to 40% can be expected, which should be detectable in a 2-arm randomized trial of 260 (for 20%) or 60 (for 40%) patients.
ISSN: 0955-3002
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Molecular Bacteriology (Rega Institute)
Laboratory of Experimental Radiotherapy
Department of Oncology - miscellaneous
× corresponding author
# (joint) last author

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