Fodstad O, Kvalheim G, Godal A, Lotsberg J, Aamdal S, Høst H, Pihl A
Cancer Res. 1984 Feb;44(2):862-5.
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.
对54例晚期癌症患者开展了一项关于蓖麻毒素（一种通过抑制蛋白质合成起作用的植物毒素）的I期研究。蓖麻毒素通过静脉推注给药，每两周一次，剂量范围为每平方米估计体表面积4.5至23微克。剂量高达每平方米18至20微克时，蓖麻毒素耐受性良好。在这些剂量水平及更高剂量时，出现了伴有疲劳和肌肉疼痛的流感样症状，部分患者还出现了恶心和呕吐。未观察到骨髓抑制现象。注射两到三次蓖麻毒素后，血清中检测到了抗蓖麻毒素抗体。蓖麻毒素按一级动力学从血液中清除。在每个剂量水平，患者之间的血浆浓度以及副作用仅显示出微小差异。给予的最高剂量为每平方米23微克，其血浆浓度是先前在荷瘤小鼠中发现具有治疗效果的浓度的两倍。在38例可评估患者中，1例淋巴瘤患者有部分缓解。4例肾癌患者、2例软组织肉瘤患者以及1例间皮瘤、甲状腺癌和直肠癌患者病情稳定。推荐每平方米23微克的剂量用于蓖麻毒素的II期试验。
