Recombinant human endostatin Phase I clinical study.doc

 PAGE \* MERGEFORMAT 8 Recombinant human endostatin Phase I clinical study Author; Tong Zhongsheng, Yan Zhao, Pakistan 1, Shu-Fen Lee, Shi Ye-hui, HE Li-hong, WANG Xu, WANG Chen, Hao Chunfang [Abstract] Objective To evaluate recombinant human endostatin in human safety and pharmacokinetic characteristics. Methods 27 cases of healthy volunteers were divided into four dose groups, respectively, 30 mg/m2 (3 Li), 60 mg/m2 (8 Li), 120 mg/m2 (8 Li), 180 mg/m2 (8 Li ), all single intravenous infusion of recombinant human endostatin; 16 cases of malignant tumor patients, sub-3 dose groups, respectively, 10 mg/m2 (10 Li), 20 mg/m2 (3 Li), 30 mg / m2 (3 cases), each continuous intravenous infusion of recombinant human endostatin 28 days; 27 cases of healthy volunteers and 10 patients with malignant tumor (10 mg/m2) with the United States Quantikine  serum immunoassay kit re - human endostatin concentration for pharmacokinetic studies. The results of the whole group no significant dose-limiting toxicity, a few occur in the heart of some toxicity, such as sinus tachycardia, myocardial ischemia, ventricular contraction, sinus arrhythmia. Other adverse reactions are rash, diarrhea, fever, fatigue. In 16 patients evaluable, MR 1 Li, SD 14 Li, PD 1 Li. Single-dose group Cmax and AUC increased linearly with the dose increased, Vd and Cl is also a corresponding increase with dose; multiple dose groups in a continuous administration of drug trough concentrations of about 1 week to reach steady-state level, used in conjunction 28 days , in the body to maintain the concentration of low and does not produce significant accumulation. Conclusion preliminary observation is effective for treatment of cancer are recommended for Phase Ⅱ clinical trials, the dose for each 10 mg/m2, day 1, continuous administration for 28 days in order to further study of this drug for cancer patients the efficacy and safety. [Keywords:] recombinant human endostatin; Ⅰ Phase I clinical studies; dos