Tonkin K S, Kelland L R, Steel G G
Radiotherapy Research Unit, Institute of Cancer Research, Sutton, Surrey, UK.
Br J Cancer. 1988 Dec;58(6):738-41. doi: 10.1038/bjc.1988.300.
The combination of irradiation and four agents of clinical interest in the treatment of cervix carcinoma (bleomycin, etoposide, cisplatin and ifosfamide) have been investigated using two human cervix carcinoma xenografts in nude mice. As a model of clinical brachytherapy regimes, radiation was administered at a continuous low dose rate of 5 cGy min-1 to a total dose of 9 or 12 Gy. No substantial enhancement in tumour growth delay over that observed for radiation alone was observed with bleomycin, etoposide or cisplatin. Ifosfamide, however, led to substantial additional growth delay, an effect which was lost when irradiation was administered at a higher dose rate of 70 cGy min-1. As dose-rates of around 5 cGy min-1 allow greater repair of radiation damage than at the higher dose-rate without significant cell cycling or repopulation, it is possible that ifosfamide may act as an inhibitor of repair processes in this model. It would be of interest to evaluate the role of ifosfamide and brachytherapy regimes in the clinical treatment of carcinoma of the cervix.
利用两种人宫颈癌裸鼠异种移植模型，研究了放疗与四种临床上用于治疗宫颈癌的药物（博来霉素、依托泊苷、顺铂和异环磷酰胺）联合使用的情况。作为临床近距离放疗方案的模型，以5 cGy min-1的连续低剂量率给予放疗，总剂量为9或12 Gy。博来霉素、依托泊苷或顺铂并未使肿瘤生长延迟较单纯放疗有显著增强。然而，异环磷酰胺导致肿瘤生长显著额外延迟，当以70 cGy min-1的较高剂量率进行放疗时，这种效应消失。由于约5 cGy min-1的剂量率比更高剂量率能使辐射损伤得到更大程度的修复，且不会有显著的细胞周期或再增殖，因此在该模型中异环磷酰胺可能作为修复过程的抑制剂发挥作用。评估异环磷酰胺和近距离放疗方案在宫颈癌临床治疗中的作用将很有意义。
