Kozin S V, Hasegawa T, Ha-Kawa S K, Akagi K, Tanaka Y
Department of Radiology, Kansai Medical University, Osaka, Japan.
Int J Radiat Oncol Biol Phys. 1994 Jun 15;29(3):505-10. doi: 10.1016/0360-3016(94)90446-4.
This study was aimed to assess the dependence on tumor size and blood flow of the efficacy of a vasoactive drug hydralazine with thermoradiotherapy.
Experiments were performed on mice bearing SCC-VII tumors with volumes of about 85 and 340 mm3 (7-8 or 11-12 days after transplantation, respectively). Local hyperthermia (water bath, 43 degrees C, 0.5 h) was started 3 h after irradiation of tumors. Hydralazine (2.5 mg/kg, IP) was given 0.5 h before heating. Tumor blood flow was evaluated by laser Doppler flowmetry before, during and up to 2 days after the treatments.
It was shown that hydralazine and hyperthermia, even in combination with each other, had very weak anti-tumor effect, especially for 85 mm tumors. The agents also insignificantly enhanced the efficacy of radiotherapy excluding the case of polyradiomodification for 340 mm3 tumors when a dose modifying factor of about 2.0 was achieved. Thermometry showed only a small improvement by HDZ in heating patterns of tumors of both sizes. Meanwhile, the therapeutic efficacy of hydralazine and heat was correlated with the changes in tumor blood flow, first of all with the delayed effects. The radiomodifiers induced only minor and transient suppression of perfusion in the smaller tumors, and more markedly and for longer time decreased blood flow in the larger tumors. In the latter case, the inhibiting effect of the drug plus hyperthermia remained for at least 48 h after the treatment.
(a) The combined use of hydralazine and heat seems to be advisable only at radiotherapy of rather large advanced tumors; (b) the efficacy of such radiomodification is correlated with prolonged inhibition of tumor blood flow by these agents; and (c) hydralazine and hyperthermia are likely to kill selectively both acutely and chronically hypoxic radioresistant cancer cells.
本研究旨在评估血管活性药物肼屈嗪与热放疗联合应用时对肿瘤大小和血流的疗效依赖性。
对分别移植7 - 8天或11 - 12天后体积约为85 mm³和340 mm³的荷SCC - VII肿瘤小鼠进行实验。肿瘤照射3小时后开始局部热疗（水浴，43℃，0.5小时）。加热前0.5小时给予肼屈嗪（2.5 mg/kg，腹腔注射）。在治疗前、治疗期间及治疗后2天内，通过激光多普勒血流仪评估肿瘤血流。
结果表明，肼屈嗪和热疗即使联合应用，抗肿瘤作用也很弱，尤其是对85 mm³的肿瘤。这些药物对放疗疗效的增强作用也不显著，但对于340 mm³的肿瘤，在实现约2.0的剂量修正因子的多放射修饰情况下除外。温度测量显示，肼屈嗪对两种大小肿瘤的加热模式仅略有改善。同时，肼屈嗪和热疗的治疗效果与肿瘤血流变化相关，首先与延迟效应相关。放射修饰剂对较小肿瘤的灌注仅引起轻微和短暂的抑制，而对较大肿瘤的血流减少更明显且持续时间更长。在后一种情况下，药物加高热的抑制作用在治疗后至少持续48小时。
（a）肼屈嗪与热疗联合使用似乎仅在对相当大的晚期肿瘤进行放疗时才可取；（b）这种放射修饰的疗效与这些药物对肿瘤血流的长期抑制相关；（c）肼屈嗪和热疗可能会选择性地杀死急性和慢性缺氧的放射抗性癌细胞。
