国产重组人白细胞介素11的Ⅰ期临床试验

Phase Ⅰ clinical trail of domestic recombinant human interleukin-11

目的 :观察国产重组人白细胞介素 11(rhIL 11)的临床不良反应 ;初步观察rhIL 11对化疗引起的血小板减少症的疗效 ;确定Ⅱ期临床试验rhIL 11的推荐剂量。方法 :对于上一个化疗周期中血小板计数最低点≤ 75× 10 9·L- 1的病人 ,于此周期化疗给药后的 2 4～ 36h皮下注射rhIL 11,qd×14d ,或血小板计数 >30 0× 10 9·L- 1后停药。rhIL 11分为 12 .5 ,2 5 ,5 0和 75 μg·kg- 1·d- 14个剂量组 ,剂量依次逐渐递增 ,每组应完成病例 3～ 5例 ,每完成一个剂量组试验后方可进行下一个剂量组试验。结果 :5 0 μg·kg- 1·d- 1剂量组有 2例病人分别出现了 3度关节肌肉疼痛和心律失常。其他不良反应均为Ⅰ～Ⅱ度 ,有发热、结膜充血、水肿、心悸、感冒样症状、恶心、呕吐、贫血、凝血因子Ⅰ升高等。 14例病人可评价疗效 ,6例 (43% )病人整个疗程中无血小板减少 ,8例有血小板减少的病人血小板最低点中位数为 80× 10 9·L- 1,从血小板最低点到恢复正常的中位时间为 4d。所有病人均不需输注血小板。结论 :rhIL 11的临床不良反应可以耐受 ,初步显示了对化疗引起的血小板减少症的疗效。Ⅱ期临床试验rhIL 11的推荐剂量为 5 0 μg·kg- 1·d- 1。

AIM: To observe the adverse reactions and effects of domestic recombinant human interleukin-11(rhIL-11) in cancer patients receiving chemotherapy, and find the recommended dose of IL-11 in phase Ⅱ trial. METHODS: Patients with chemotherapy-induced thrombocytopenia(PLT nadir≤ 75×109·L -1) in prechemotherapy cycle were enrolled into this study. Twenty-four to 36 h after completion of study chemotherapy cycle, rhIL-11 was SC injected, qd for 14 d, or discontinued if platelet count was>300×109·L -1. Cohorts of 3 to 5 patients were accrued to 4 dose levels of rhIL-11(12.5, 25, 50 and 75 μg·kg -1·d -1). Dosage escalated from lower level to higher. Three to 5 patients should be studied in every cohort. The higher dosage level study should not start until the lower dose level study had finished. RESULTS:Fifteen patients entered into the study. Grade 3 adverse reactions (arrhythmia and arthralgias)were seen in 2 patients at dose of 50 μg·kg -1·d -1, and administration of study drug stopped in this 2 patients. Other adverse reactions related to rhIL-11(fever, conjectival injection, edema, palpitations, flu-like symptom and anemia) were mild to moderate(Grade 1 to 2). Fourteen patients efficacy was evaluated. Thrombocytopenia did not occur during the study cycle in 6 patients. Median platelet nadir was 80×109·L -1 in 8 patients with thrombocytopenia. Median time to platelet recovery was 4 d. None patient required platelet transfusion. CONCLUSION: RhIL-11 is well tolerated at doses of 12.5, 25 and 50 μg·kg -1·d -1. Dose of 50 μg·kg -1·d -1 has the potential activity to reduce chemotherapy-induced thrombocytopenia. The recommended dose of rhIL-11 is 50 μg·kg -1·d -1 in phase Ⅱ trail.