Distelmans W, Van Ginckel R, Vanherck W, Willebrords R, Wouters L, De Brabander M, Mesens J
Janssen Research Foundation, Beerse, Belgium.
Anticancer Res. 1991 Jan-Feb;11(1):253-6.
The clinically applicable formulation of the microtubule inhibitor erbulozole (R 55 104), dissolved into an aqueous hydroxypropyl-beta-cyclodextrin solution (designated as R 55 104-CYCLO), exerts a similar effect on growth delay of subcutaneous MO4 fibrosarcomas in mice, with or without 10 Gy gamma-irradiation given locally to the tumors 2 h later, compared to R 55 104 in water. The drug concentration can be reduced from 80 mg/kg to 5 mg/kg without affecting the activity of this particular drug-radiation combination. Furthermore, 80 mg/kg R 55 104-CYCLO show a radioprotective effect when given 2 h before total body irradiation of non-tumor bearing mice. A radiation dose of 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 Gy respectively was given resulting in a LD50(30) of 5.97 Gy for the irradiated mice and 7.65 Gy for the drug-radiation treated animals (Dose Effect Factor = 0.78). Therapeutic implications of both observations are discussed.
微管抑制剂厄布洛唑（R 55 104）的临床适用制剂溶解于羟丙基-β-环糊精水溶液（命名为R 55 104-CYCLO）中，与水中的R 55 104相比，无论在肿瘤局部2小时后是否给予10 Gy的γ射线照射，其对小鼠皮下MO4纤维肉瘤生长延迟的影响相似。药物浓度可从80 mg/kg降至5 mg/kg，而不影响这种特定药物-辐射组合的活性。此外，在对无肿瘤小鼠进行全身照射前2小时给予80 mg/kg R 55 104-CYCLO可显示出辐射防护作用。分别给予1、2、3、4、5、6、7、8、9或10 Gy的辐射剂量，导致照射小鼠的LD50(30)为5.97 Gy，药物-辐射治疗动物的LD50(30)为7.65 Gy（剂量效应因子 = 0.78）。讨论了这两种观察结果的治疗意义。
