Clinical testing of the radiosensitizer Ro 07-0582: experience with multiple doses.
Clinical testing of the radiosensitizer Ro 07-0582: experience with multiple doses.
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DOI：
10.1038/bjc.1977.90
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发表时间：
1977-05
影响因子：
8.8
通讯作者：
Flockhart, I R
中科院分区：
文献类型：
--
作者：
Dische, S;Saunders, M I;Lee, M E;Adams, G E;Flockhart, I R
低氧细胞放射增敏剂Ro 07-0582现已多次给予16名患者。他们总共接受了3-20剂15-51克。即刻耐受性良好，并且始终获得令人满意的药物血浆水平。然而，神经毒性是一个棘手的问题：在给予最高剂量的患者中发生了惊厥，11例患者出现了周围神经病变。在人类肿瘤中获得的肿瘤浓度与血浆浓度相似，而在小鼠肿瘤中的发现则相反，小鼠肿瘤中的浓度通常低于血浆水平的40%。在人类肿瘤的治疗中，较低剂量的Ro 07-0582应该产生有用的低氧细胞致敏作用。虽然Ro 07-0582的总剂量必须受到限制，但它在临床放射治疗中具有真实的前景。
The hypoxic cell radiosensitizer, Ro 07-0582, has now been given in multiple doses to 16 patients. They have received a total of 15-51 g in 3-20 doses. Immediate tolerance was good, and satisfactory plasma levels of the drug were consistently obtained. Neurotoxicity was, however, troublesome: convulsions occurred in the patient given the highest dose, and there was peripheral neuropathy in 11 cases. Tumour concentrations similar to those in plasma were obtained in human tumours, in contrast to the findings in mouse tumours where concentrations are usually below 40% of plasma levels. In the treatment of human tumours, a lower dose of Ro 07-0582 should give useful hypoxic cell sensitization. Although the total dose of Ro 07-0582 must be limited, there is a real prospect that it will give benefit in clinical radiotherapy.