Wagstaff J, Smith D, Nelmes P, Loynds P, Crowther D
Cancer Immunol Immunother. 1987;25(1):54-8. doi: 10.1007/BF00199301.
Human recombinant DNA interferon gamma (IFN-G), with a specific activity of 2 X 10(6) IU/mg protein, was administered s.c. 3 days per week for 2 months to patients with solid tumors. The maximum tolerated dose (MTD) was 10 X 10(6) IU/m2 (5.0 mg/m2) per injection, and six patients were treated at the MTD. Two of these ceased treatment because of severe subjective toxicity (headache, rigors and pyrexia) and three patients developed WHO grade 3 leucopenia. Subjective toxicity varied considerably between patients and some patients at low dose levels experienced severe constitutional symptoms whilst others treated at the MTD had few side effects. These differences were unrelated to pharmacokinetic parameters. Bioavailability of this IFN-G administered s.c. was very variable from one patient to another at the same dose level. We therefore counsel caution in using this IFN-G preparation s.c. in phase II studies.
将比活性为2×10⁶IU/mg蛋白质的重组人DNA干扰素γ（IFN-G），以每周3天的频率皮下注射给实体瘤患者，持续2个月。最大耐受剂量（MTD）为每次注射10×10⁶IU/m²（5.0mg/m²），6名患者接受了MTD剂量的治疗。其中2名患者因严重的主观毒性（头痛、寒战和发热）而停止治疗，3名患者出现了世界卫生组织3级白细胞减少症。患者之间的主观毒性差异很大，一些低剂量水平的患者出现了严重的全身症状，而其他接受MTD治疗的患者副作用很少。这些差异与药代动力学参数无关。在相同剂量水平下，这种皮下注射的IFN-G在不同患者之间的生物利用度差异很大。因此，我们建议在II期研究中谨慎使用这种皮下注射的IFN-G制剂。
