Creaven P J, Plager J E, Dupere S, Huben R P, Takita H, Mittelman A, Proefrock A
Department of Clinical Pharmacology and Therapeutics, Roswell Park Memorial Institute, New York State Department of Health, Buffalo 14263.
Cancer Chemother Pharmacol. 1987;20(2):137-44. doi: 10.1007/BF00253968.
A phase I and pharmacokinetic study of recombinant tumor necrosis factor (rH-TNF Asahi) was carried out in 29 patients, who received a total of 72 courses with doses ranging from 1 to 48 X 10(4) units/m2. Drug was given as 1-h i.v. infusions. Acute toxicities, taking the form of fever, chills, tachycardia, hypertension, peripheral cyanosis, nausea and vomiting, headache, chest tightness, low back pain, diarrhea and shortness of breath were seen, but were not dose-limiting or dose-related. Some early rise in SGOT, without any change in serum bilirubin, was noted at the highest doses. Eosinophilia, monocytosis, mild hypocalcemia and an increase in fibrin degradation products were seen in a few patients. The dose-limiting toxicity was hypotension, which occurred after the end of the drug infusion and was seen in all 5 patients treated at the highest dose. There was no mortality or long-term morbidity. There were no responses. Pharmacokinetic studies indicated a rapid plasma clearance and a short plasma half-life, generally less than 0.5 h.
对29例患者进行了重组肿瘤坏死因子（rH-TNF 旭化成）的I期和药代动力学研究，这些患者共接受了72个疗程，剂量范围为1至48×10⁴单位/平方米。药物通过1小时静脉输注给药。观察到急性毒性表现为发热、寒战、心动过速、高血压、外周发绀、恶心、呕吐、头痛、胸闷、腰痛、腹泻和呼吸急促，但这些毒性并非剂量限制性或与剂量相关。在最高剂量时，观察到谷草转氨酶（SGOT）有一些早期升高，而血清胆红素无任何变化。少数患者出现嗜酸性粒细胞增多、单核细胞增多、轻度低钙血症和纤维蛋白降解产物增加。剂量限制性毒性为低血压，发生在药物输注结束后，在接受最高剂量治疗的所有5例患者中均有出现。无死亡或长期发病情况。未观察到反应。药代动力学研究表明血浆清除迅速，血浆半衰期短，一般小于0.5小时。
