Ludwig C U, Ludwig-Hagemann R, Obrist R, Obrecht J P, Holdener E E, Sutter-Melde C
Department of Internal Medicine, The University, Kantonsspital Basle, Switzerland.
Onkologie. 1990 Apr;13(2):117-22. doi: 10.1159/000216737.
Fifteen patients with progressing melanomas, hypernephromas or B-cell malignancies were treated in a phase I study with Interferon (IFN) alpha-2a by continuous subcutaneous infusion. With the help of a syringe driver pump daily doses of 12-15 MU resulting in median weekly doses of 90 MU could be safely given with little side effects. Flu-like symptoms and side effects from the gastrointestinal tract were mainly of grade 1 or 2 only. The major dose limiting but reversible toxicity was leukopenia. Five patients developed local inflammatory reactions at the infusion site. The pharmacokinetic data demonstrate that by this route of administration median serum levels of 54 IU/ml (range 9.6-192.0 IU/ml) (EIA-F-assay) can be achieved. Antibody formation was observed in 4 patients. - One out of 9 patients evaluable for tumor response demonstrated a partial tumor regression and 4 patients had a stabilisation of their disease. In comparison to intermittent i.m. or s.c. schedules, this novel route of administration by continuous subcutaneous infusion results in significant serum concentrations, biological activity and little clinical side effects. This may facilitate in the future the combination of IFN alpha-2a with other biological response modifiers like interleukin-2 or tumor necrosis factor.
在一项I期研究中，对15例进展期黑色素瘤、肾细胞癌或B细胞恶性肿瘤患者采用皮下持续输注干扰素（IFN）α-2a进行治疗。借助注射泵，每日剂量12 - 15 MU，中位每周剂量90 MU，可安全给药，且副作用轻微。流感样症状和胃肠道副作用主要仅为1级或2级。主要的剂量限制性但可逆的毒性是白细胞减少。5例患者在输注部位出现局部炎症反应。药代动力学数据表明，通过这种给药途径可实现中位血清水平54 IU/ml（范围9.6 - 192.0 IU/ml）（酶免疫分析F法）。4例患者观察到抗体形成。 - 9例可评估肿瘤反应的患者中有1例出现部分肿瘤消退，4例患者病情稳定。与间歇性肌内或皮下给药方案相比，这种新型的皮下持续输注给药途径可产生显著的血清浓度、生物活性且临床副作用轻微。这可能在未来有助于干扰素α-2a与其他生物反应调节剂如白细胞介素-2或肿瘤坏死因子联合使用。
