9-硝基喜树碱的Ⅰ期临床试验  

A phaseⅠclinical trial of 9-nitrocamptothecin:tolerance and safety evaluation

作　　者：杨华[1] 王华庆[1] 阎昭[1] 孙琦 朱宇江 

机构地区：[1]天津医科大学附属肿瘤医院内一科,天津300060 [2]上海艾斯可生物技术有限公司,上海200433

出　　处：《中国新药杂志》2007年第10期802-805,809,共5页Chinese Journal of New Drugs

基　　金：国家高技术研究发展计划(863计划)课题(2004AA2Z3721)

摘　　要：目的:观察9-硝基喜树碱(9-nitrocamptothecin,9-NC)在肿瘤患者中单次和多次口服给药的安全性和耐受性,并初步观察该药的抗肿瘤作用。方法:采取先单次后连续给药,先低剂量后高剂量的逐级递增的探索性试验方法。单次组:32例恶性肿瘤患者,分5组,分别给予9-NC 1．0,1．25,1．5,1．75,2．0mg·m^(-2),单次口服。观察患者的耐受性及用药后d 3,d 7的血尿常规、生化指标、凝血功能及心电图等。连续组:13例恶性肿瘤患者分3组,分别给予国产9-NC 1．25．1．5,1．75 mg·m^(-2)·d^(-1),口服5 d停2 d,共3周,观察耐受性及d 3,d 10,d 17,d 28的各种化验检查,评估治疗前后肿瘤体积的变化,血清肿瘤标志物水平和生活质量的改善及生存率。结果:单次组不良反应有恶心、贫血、白细胞减低、血尿、腹泻、转氨酶升高等。连续组不良反应有乏力、白细胞减低、恶心呕吐、反酸、腹泻、转氨酶升高、血尿等。1．75 mg·m^(-2)·d^(-1)组出现Ⅱ度呕吐和Ⅱ度骨髓抑制,恶心呕吐为剂量限制性毒性反应。结论:9-NCⅡ期临床试验单次和连续给药推荐剂量分别为1．75和1．5 mg·m^(-2)·d^(-1)。Objective： To evaluate the tolerance and safety of 9-nitrocamptothecin （9-NC）.Methods： Thirty-two patients with malignant cancers were randomized to receive a single oral dose of 9- NC 1.0, 1.25, 1.5, 1.75 or 2.0 mg. m^-2. The tolerance and safety of 9-NC were assessed based on changes of blood and urinary tests, function of blood coagulation and electrocardiogram at the end of the day 3 and 7 after the administration of 9-NC. Additional 13 patients with malignant cancers were randomly given with an ascending dose of 9-NC 1.25,1.5 or 1.75 mg.m^-2 once daily for 5 days plus 2-day rest per cycle, total 3 cycles. The tolerance and laboratory examinations were evaluated at day 3, 10, 17 and 28 after the 9NC administration. Other endpoints were to assess the tumor size by CT, the levels of tumor markers and improvement of quality of life before and after the therapy. Results： The adverse events patients receiving single dose experienced included nausea, anemia, leucopenia, hematuria and diarrhea. The patients receiving ascending doses had fatigue, leukopenia, nausea and vomit; sour regurgitation, hematuria, diarrhea, bloody urine and abnormal escalation of transaminase. The patients at the dose of 1.75 mg.m^-2, d^-1 suffered from grade lI nausea and vomit and myelosuppression. Conclusion： The recommended phase II single or successive doses of 9NC is 1. 75 mg. m^-2 and 1.5 mg.m^-2.d^-l, respectively.

关 键 词：9-硝基喜树碱 I期临床试验 耐受性 

分 类 号：R73[医药卫生—肿瘤] R979.1[医药卫生—临床医学]