Davis I D, Maher D W, Cebon J S, Green M D, Fox R M, McKendrick J J, Rybak M E, Boyd A W
Ludwig Institute for Cancer Research, Melbourne, Australia.
Growth Factors. 2000;17(4):287-300. doi: 10.3109/08977190009028972.
To investigate the pharmacokinetics and tolerability of recombinant human interleukin-4 (rhuIL-4), administered by daily subcutaneous injection, in patients with advanced cancer.
Fourteen patients with advanced cancer treated with rhuIL-4 at escalating dose levels of 0.25, 1.0 and 5.0 microg/kg/day, on days 1, 8-17, and 28-57. The primary endpoints of the study were toxicity of rhuIL-4 and the determination of the pharmacokinetics of rhuIL-4 when given by subcutaneous injection. Secondary endpoints included effects on blood counts, hematopoietic cell precursors, and various immunologic parameters.
rhuIL-4 was well tolerated at all three dose levels. Detectable serum levels of IL-4 were found in patients at the 1.0 and 5.0 microg/kg/day dose levels. Peak serum IL-4 levels were achieved about 2 h after injection and IL-4 was still detectable 8 h after injection. No grade 4 toxicities were observed and grade 3 toxicities were confined to fever, headache and raised hepatic alkaline phosphatase. No consistent hematological or immunologic effects were observed. Although therapeutic efficacy was not an endpoint, one complete response (Hodgkin's disease) was observed. One patient with chronic lymphocytic leukemia progressed on therapy.
rhuIL-4 up to 5.0 microg/kg/day is well tolerated when given by subcutaneous injection. Biologically relevant serum IL-4 levels can be achieved and sustained for at least 8 h after a single injection.
研究每日皮下注射重组人白细胞介素-4（rhuIL-4）在晚期癌症患者中的药代动力学和耐受性。
14例晚期癌症患者接受rhuIL-4治疗，剂量分别为0.25、1.0和5.0μg/kg/天，于第1天、第8 - 17天和第28 - 57天逐步递增剂量。本研究的主要终点是rhuIL-4的毒性以及皮下注射rhuIL-4时的药代动力学测定。次要终点包括对血细胞计数、造血细胞前体和各种免疫参数的影响。
在所有三个剂量水平下，rhuIL-4耐受性良好。在1.0和5.0μg/kg/天剂量水平的患者中检测到可检测的血清IL-4水平。注射后约2小时达到血清IL-4峰值水平，注射后8小时仍可检测到IL-4。未观察到4级毒性，3级毒性仅限于发热、头痛和肝碱性磷酸酶升高。未观察到一致的血液学或免疫学效应。尽管治疗效果不是终点，但观察到1例完全缓解（霍奇金病）。1例慢性淋巴细胞白血病患者在治疗过程中病情进展。
皮下注射rhuIL-4高达5.0μg/kg/天时耐受性良好。单次注射后可达到并维持至少8小时的生物学相关血清IL-4水平。
