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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 observe the safety and tolerability of 9-nitrocamptothecin (9-NC) in single and multiple oral administrations in cancer patients and to observe its anti-tumor effect. Methods: The first consecutive single-dose administration, the first low-dose high-dose incremental exploration test method. A single group: 32 patients with malignant tumor, divided into 5 groups, were given 9-NC 1.0,1.25,1.5,1.75,2.0 mg · m -2, a single oral. Observe the patient’s tolerance and medication d 3, d 7 hematuria, biochemical indicators, coagulation and ECG. Continuous group: 13 patients with malignant tumor were divided into 3 groups, which were given domestic 9-NC 1.25.1.5,1.75 mg · m -2 · d -1, d for 3 weeks to observe the tolerability and d 3, d 10, d 17, d 28 various laboratory tests to assess changes in tumor volume before and after treatment, serum tumor markers and quality of life improvement and survival rate. Results: A single group of nausea and adverse reactions, anemia, leukopenia, hematuria, diarrhea, elevated transaminases. Continuous adverse reactions were fatigue, leukopenia, nausea and vomiting, acid reflux, diarrhea, elevated transaminases, hematuria and so on. In the group of 1.75 mg · m -2 d -1, grade Ⅱ vomiting and grade Ⅱ myelosuppression were observed. Nausea and vomiting were dose-limiting toxicities. CONCLUSION: The recommended doses for single-dose and continuous administration of 9-NC Phase II clinical trials are 1.75 and 1.5 mg · m -2 · d -1, respectively.