Hong S S, Abe Y, Kaneta K, Matsuzawa T
Int J Radiat Oncol Biol Phys. 1984 Dec;10(12):2369-73. doi: 10.1016/0360-3016(84)90247-5.
The radiosensitizing effect of misonidazole is dose dependent, so theoretically it would be desirable to use as large a dose as possible. However, clinical studies have indicated a maximum tolerable dose restricting the effects of misonidazole in patients. We injected misonidazole directly into tumor tissues in combination with irradiation in an attempt to obtain a sufficiently high concentration in tumors while maintaining a low level in the blood. Concentration of the drug in tumor tissues was confirmed to be high by examination of the resected low-grade chondrosarcoma into which the drug had been locally injected prior to the operation. Blood levels were confirmed to be significantly low. Seventeen patients were treated with local injections of the drug, each with radiotherapy. All patients either had advanced tumors, or were in the terminal stage after repeated radiotherapy and chemotherapy. A relatively high radiation dose per fraction was used. Complete response was obtained in eight patients (47%) and partial response in four (24%). No change was observed in three patients (18%) while two (12%) exhibited progressive disease. In the seven patients with multiple metastatic lesions, the response of the tumors treated with this method were compared to that of the tumors treated by radiation alone in the same patient. The sensitizing effect of the drug was clearly observed in three out of seven patients. No toxicities in the nervous system or in the gastrointestinal system were observed, and no local skin damage by the injections was seen. Local injections of misonidazole were shown to have a significant radiosensitizing effect without any side effects. The combined treatment of radiation and local injections of misonidazole is considered to be a promising new treatment method.
米索硝唑的放射增敏作用具有剂量依赖性，因此从理论上讲，使用尽可能大的剂量是可取的。然而，临床研究表明存在最大耐受剂量，这限制了米索硝唑在患者中的作用。我们将米索硝唑直接注射到肿瘤组织中并结合放疗，试图在肿瘤中获得足够高的浓度，同时保持血液中的低水平。通过对术前局部注射该药物的切除的低度软骨肉瘤进行检查，证实肿瘤组织中的药物浓度很高。血液水平经证实显著较低。17例患者接受了该药物的局部注射，均接受了放疗。所有患者要么患有晚期肿瘤，要么在反复放疗和化疗后处于终末期。采用了相对较高的每次分割放疗剂量。8例患者（47%）获得完全缓解，4例（24%）获得部分缓解。3例患者（18%）无变化，2例（12%）疾病进展。在7例有多处转移灶的患者中，将用这种方法治疗的肿瘤的反应与同一患者中单独放疗治疗的肿瘤的反应进行了比较。7例患者中有3例明显观察到了该药物的增敏作用。未观察到神经系统或胃肠道系统的毒性反应，也未见到注射引起的局部皮肤损伤。米索硝唑局部注射显示出显著的放射增敏作用且无任何副作用。放疗与米索硝唑局部注射联合治疗被认为是一种有前景的新治疗方法。
