Phase I study of the plant protein ricin.
Phase I study of the plant protein ricin.
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DOI：
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发表时间：
1984-02
期刊：
影响因子：
11.2
通讯作者：
Ø. Fodstad;Gunnar Kvalheim;A. Godal;Jostein Lotsberg;Steinar Aamdal;Herman Høst;Alexander Pihl
中科院分区：
文献类型：
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作者：
Ø. Fodstad;Gunnar Kvalheim;A. Godal;Jostein Lotsberg;Steinar Aamdal;Herman Høst;Alexander Pihl
蓖麻毒素（一种通过抑制蛋白质合成发挥作用的植物毒素）对 54 名晚期癌症患者进行了一项 I 期研究。蓖麻毒素以静脉注射方式给予。每两周进行一次推注，剂量范围为 4.5 至 23 微克/平方米估计体表面积。蓖麻毒素在剂量高达 18 至 20 微克/平方米时具有良好的耐受性。在这些水平和更高水平上，出现了类似流感的症状，包括疲劳和肌肉疼痛，并且在一些患者中还出现了恶心和呕吐。没有观察到骨髓抑制。注射两到三次蓖麻毒素后，在血清中检测到了蓖麻毒素抗体。根据一级动力学，蓖麻毒素从血液中消除。在每个剂量水平下，患者之间的血浆浓度以及副作用仅存在微小差异。给予的最高剂量为 23 微克/平方米，血浆浓度是之前发现的对荷瘤小鼠治疗有效的浓度的两倍。在 38 名可评估的患者中，一名淋巴瘤患者出现部分缓解。在四名肾癌患者、两名软组织肉瘤患者以及一名间皮瘤、甲状腺癌和直肠癌患者中观察到病情稳定。蓖麻毒素 II 期试验建议剂量为 23 微克/平方米。
A Phase I study was carried out with ricin, a plant toxin acting by inhibiting protein synthesis, on 54 cancer patients with advanced disease. Ricin was given as i.v. bolus injections every two weeks at dose levels ranging from 4.5 to 23 micrograms/sq m of estimated body surface area. Ricin was well tolerated at doses up to 18 to 20 micrograms/sq m. At these levels and at higher levels, flu-like symptoms with fatigue and muscular pain appeared and, in some patients, nausea and vomiting occurred also. No myelo-suppression was seen. Antibodies to ricin were detected in serum after two to three ricin injections. Ricin was eliminated from blood according to first order kinetics. At each dose level, the plasma concentrations, as well as the side effects, showed only minor differences between patients. The highest dose given, 23 micrograms/sq m, gave plasma concentrations twice those found previously to be therapeutically effective in tumor-bearing mice. Of 38 evaluable patients, one patient with lymphoma had a partial response. Stable disease was observed in four patients with renal cancers, in two with soft tissue sarcomas, and in one patient each with mesothelioma, thyroid, and rectal cancer. A dose of 23 micrograms/sq m is recommended for Phase II trials of ricin.