Stone H B
Department of Radiation Oncology, University of California, San Francisco 94143.
Int J Radiat Oncol Biol Phys. 1988 May;14(5):957-62. doi: 10.1016/0360-3016(88)90018-1.
The potential therapeutic benefit of misonidazole was tested in radiotherapy with 1, 2, 5, and 10 equal fractions, using as endpoints local tumor control (TCD50) of murine mammary carcinoma MDAH-MCa-4 and leg contracture at the TCD50, measured 120 days after irradiation. In controls and misonidazole-treated mice, the TCD50 increased with the number of fractions, from 66.7 to 114.6 Gy in controls, and from 43.3 to 75.7 Gy with misonidazole. At doses of greater than or equal to 0.1 mg/g body weight, misonidazole reduced the TCD50 in all fractionation schedules; however, because of toxicity, 1.0 and 0.6 mg/g could be given with only 1 or 2 fractions. Leg contracture at the TCD50 was greatest (14.5 mm) in control mice treated with a single dose of radiation, and was least (7.2 to 7.4 mm) in those treated with a single dose of radiation preceded by 1.0 or 0.6 mg misonidazole/g body weight. With 0.1 mg misonidazole/g, the leg contracture at the TCD50 was less (9.8 to 12.2 mm with the various schedules) than in controls (12.0 to 14.5 mm) for 1, 5, or 10 fractions. Therefore, a therapeutic gain could be obtained by using misonidazole with 1, 2, 5, or 10 fractions, but the greatest gain occurred with 1 fraction, with high doses of misonidazole, that is, 0.6 to 1.0 mg/g.
在放射治疗中，使用1、2、5和10个相等分次剂量来测试米索硝唑的潜在治疗益处，将小鼠乳腺癌MDAH-MCa-4的局部肿瘤控制（TCD50）以及在TCD50时的腿部挛缩作为终点指标，在照射后120天进行测量。在对照组和米索硝唑治疗组小鼠中，TCD50随分次剂量的增加而升高，对照组从66.7 Gy升至114.6 Gy，米索硝唑治疗组从43.3 Gy升至75.7 Gy。在剂量大于或等于0.1 mg/g体重时，米索硝唑在所有分次方案中均降低了TCD50；然而，由于毒性，1.0 mg/g和0.6 mg/g只能与1或2个分次剂量一起给药。在接受单次辐射治疗的对照小鼠中，TCD50时的腿部挛缩最大（14.5 mm），而在接受1.0 mg或0.6 mg米索硝唑/g体重预处理后再接受单次辐射治疗的小鼠中，腿部挛缩最小（7.2至7.4 mm）。使用0.1 mg米索硝唑/g时，对于1、5或10个分次剂量，TCD50时的腿部挛缩（在不同方案中为9.8至12.2 mm）低于对照组（12.0至14.5 mm）。因此，使用米索硝唑与1、2、5或10个分次剂量联合使用可获得治疗增益，但最大增益出现在1个分次剂量且使用高剂量米索硝唑（即0.6至1.0 mg/g）的情况下。
