Milas L, Ito H, Nakayama T, Hunter N
Department of Experimental Radiotherapy, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Cancer Res. 1991 Jul 15;51(14):3639-42.
In this study we asked whether the improvement in the therapeutic ratio of radiotherapy by indomethacin (INDO), which potentiates tumor radioresponse through stimulation of the immune system, could be further improved by combining it with the hypoxic cell radiosensitizer misonidazole (MISO). Mice bearing the syngeneic sarcoma fibrosarcoma (8 mm) in the leg were treated with single graded doses of gamma-rays to the tumor or with irradiation combined with INDO, MISO, or both drugs. Local tumor control was the end point of tumor radioresponse. In addition, the effect of these drugs on radiation-caused hair loss and leg contractures was assessed. INDO increased tumor radioresponse by a factor of 1.31, but it did not affect either hair loss or leg contractures. MISO increased tumor radioresponse by a factor of 1.86, hair loss by a factor of 1.69, and leg contractures by a factor of 1.54, thus providing only a small therapeutic gain. The combined INDO plus MISO treatment increased tumor radioresponse by a factor of 2.72, which was more than the additive effect of the individual drugs. On the other hand, the combined treatment caused no additional hair loss compared to that caused by MISO only. Overall, our results show that INDO plus MISO treatment increased tumor radioresponse more than INDO or MISO alone and provided a significant therapeutic gain. Furthermore, they illustrate that combinations of two radiopotentiating agents with different mechanisms of action may improve the radiotherapeutic effect.
在本研究中，我们探讨了吲哚美辛（INDO）通过刺激免疫系统增强肿瘤放射反应从而提高放射治疗治疗比的效果，是否能通过将其与乏氧细胞放射增敏剂米索硝唑（MISO）联合使用而进一步提高。对腿部患有同基因纤维肉瘤（8毫米）的小鼠，给予肿瘤单剂量梯度γ射线照射，或照射联合INDO、MISO或两种药物。局部肿瘤控制是肿瘤放射反应的终点。此外，还评估了这些药物对辐射引起的脱发和腿部挛缩的影响。INDO使肿瘤放射反应提高了1.31倍，但对脱发或腿部挛缩均无影响。MISO使肿瘤放射反应提高了1.86倍，脱发提高了1.69倍，腿部挛缩提高了1.54倍，因此仅提供了较小的治疗增益。INDO加MISO联合治疗使肿瘤放射反应提高了2.72倍，超过了单独使用各药物的相加效应。另一方面，与仅使用MISO相比，联合治疗未导致额外的脱发。总体而言，我们的结果表明，INDO加MISO联合治疗比单独使用INDO或MISO更能提高肿瘤放射反应，并提供显著的治疗增益。此外，它们还表明，两种作用机制不同的放射增效剂联合使用可能会提高放射治疗效果。
