Stone H B, Luu Y H, Lam K N
Int J Radiat Oncol Biol Phys. 1986 Jul;12(7):1097-100. doi: 10.1016/0360-3016(86)90234-8.
The primary toxicity of Ro 03-8799 is a central nervous system toxicity, whereas that of SR-2508 is a peripheral neuropathy. The feasibility of reducing overall toxicity while maintaining maximal radiosensitization by using the two sensitizers together was tested. The LD50/2 of Ro 03-8799 was 0.68 mg/g body wt (mg/gbw) after intravenous (i.v.) administration, and that of SR-2508 was 4.4 mg/gbw after i.v. administration. When both drugs were given together in equitoxic proportions, the LD50/2 was 0.45 mg of Ro 03-8799 plus 2.9 mg of SR-2508/gbw. These doses are 66% of the respective LD50/2 values of the drugs when given separately. Radiosensitization was evaluated using in vivo-in vitro assays with EMT6/SF tumors in BALB/c mice. At drug doses between 10 and 60% of the LD50/2, sensitization was generally maximal and similar to that from misonidazole, but there was less sensitization below this dose, both with the drugs given separately and together. If chronic toxicities of these drugs overlap as do the acute toxicities there will be little or no additional benefit from using these drugs in combination, compared to using them separately.
Ro 03-8799的主要毒性是中枢神经系统毒性，而SR-2508的主要毒性是周围神经病变。研究了联合使用这两种增敏剂在保持最大放射增敏作用的同时降低总体毒性的可行性。静脉注射后，Ro 03-8799的半数致死剂量/2（LD50/2）为0.68毫克/克体重（mg/gbw），SR-2508静脉注射后的LD50/2为4.4 mg/gbw。当两种药物以等毒性比例联合给药时，LD50/2为0.45毫克Ro 03-8799加2.9毫克SR-2508/gbw。这些剂量分别是两种药物单独给药时LD50/2值的66%。使用BALB/c小鼠的EMT6/SF肿瘤通过体内-体外试验评估放射增敏作用。在药物剂量为LD50/2的10%至60%之间时，增敏作用通常最大且与甲硝唑相似，但低于此剂量时，无论是单独给药还是联合给药，增敏作用都较小。如果这些药物的慢性毒性与急性毒性一样重叠，那么与单独使用这些药物相比，联合使用这些药物几乎不会有额外益处。
