Lambin P, Nuyts S, Landuyt W, Theys J, De Bruijn E, Anné J, Van Mellaert L, Fowler J
University Hospital Gasthuisberg, Department of Radiation Oncology, Leuven, Belgium.
Int J Radiat Biol. 2000 Mar;76(3):285-93. doi: 10.1080/095530000138628.
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.
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.
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.
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.
评估在用胞嘧啶脱氨酶（CD）基因转导的肿瘤中，转化为5-氟尿嘧啶（5-FU）所需的5-氟胞嘧啶（5-FC）浓度，以实现对放疗具有临床显著意义的放射增敏作用。
从每次2 Gy分割、总剂量66 Gy的放疗的肿瘤控制概率（TCP）为37%开始，估计从增敏比（SER）为1.1、1.2等预期的TCP增加情况。5-FU的SER值通过文献综述获得。还对5-FC的临床毒性进行了综述。
据报道，如果每次照射后在周围介质中维持0.6 - 0.9μg/ml的浓度数天，5-FU是一种有效的放射增敏剂。在标准抗真菌治疗中，患者对浓度为25 - 100μg/ml（平均60μg/ml）的5-FC耐受良好，持续6周。如果5-FC的转化效率为1 - 3%，应可获得足够的5-FU。每日2 Gy分割时，SER值应可达到1.1至1.2。对体外和异种移植实验进行了综述，它们与结论不矛盾。
预计肿瘤控制率可提高20%至40%，这在一项260名患者（提高20%）或60名患者（提高40%）的双臂随机试验中应可检测到。
