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目的:观察注射用紫杉肽(paclitaxtide)在人体的安全性,确定紫杉肽静脉给药对晚期恶性肿瘤患者的最大耐受剂量(MTD)及剂量限制性毒性(DLT),为Ⅱ期临床研究提供安全有效的给药剂量及方案。方法:选择符合病例入选标准的受试者,采用改良的Fibonacci法进行剂量爬坡,起始剂量60 mg.m-2,每剂量组3例,逐渐爬升,出现DLT增至6例,一个剂量组出现2例DLT,终止试验。患者接受单次静脉给药,观察不良反应,给药d 21进行疗效评价。结果:入组晚期恶性肿瘤患者33例,剂量自60 mg.m-2升至420mg.m-2,共10个剂量组。紫杉肽最常见的毒性是骨髓抑制,白细胞、中性粒细胞、血红蛋白、血小板减少,DLT为IV度中性粒细胞减少;其他不良反应包括转氨酶升高、恶心、呕吐、疲乏、食欲下降,高剂量组出现周围神经毒性,主要是I度和II度。疗效评价部分缓解1例,稳定17例,进展15例。结论:IV度中性粒细胞减少为紫杉肽主要剂量限制性毒性,最大耐受剂量390 mg.m-2,推荐给II期临床研究的安全剂量为360mg.m-2,d1,21 d为1个周期。
OBJECTIVE: To observe the safety of injectable paclitaxtide in human and to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of intravenous injection of paclitaxel in patients with advanced malignancies. Research to provide safe and effective dosage and program. Methods: Subjects who met the criteria of the case selection were screened by the modified Fibonacci method. The initial dose was 60 mg.m-2, and in each dose group, 3 patients gradually climbed up. The DLT increased to 6 patients and one dose Two DLTs occurred in the group and the trial was terminated. Patients received a single intravenous administration, observed adverse reactions, d 21 administered efficacy evaluation. Results: Thirty-three patients with advanced malignant tumor were enrolled in this study. The dose of 60 patients was increased from 60 mg.m-2 to 420 mg.m-2 in 10 doses. The most common toxicity of paclitaxel is myelosuppression, leukocyte, neutrophil, hemoglobin, thrombocytopenia, DLT neutropenia IV; other adverse reactions include elevated aminotransferases, nausea, vomiting, fatigue, loss of appetite, Peripheral neurotoxicity occurred in the high-dose group, mainly I degrees and II degrees. Efficacy evaluation of partial response in 1 case, stable in 17 cases, progress in 15 cases. Conclusions: IV neutropenia is the major dose-limiting toxicity of paclitaxel, with a maximum tolerated dose of 390 mg.m-2 and a safe dose of 360 mg.m-2 recommended for phase II clinical studies, d1 and 21 d For 1 cycle.