【摘要】 目的:评价氮烯苯酸(DM-PTA)对常见恶性肿瘤的抗瘤活性和各系统毒性反应。方法:根据临床前动物实验结果推算,I期临床试验起始剂量为80mg/m2,根据Fibonaci法递增剂量,直至找到MTD,MTD低一级剂量为推荐Ⅱ期临床试验的剂量。结果:求得MTD为2000mg/m2静脉灌注5天,剂量限制性毒性为恶心呕吐。推荐Ⅱ期临床试验剂量为1600mg/m2×5天,每3周重复。Ⅱ期临床试验共收治晚期恶性肿瘤患者59例,其中非小细胞肺癌25例、小细胞肺癌5例、非霍奇金淋巴瘤(NHL)7例,霍奇金病(HD)5例,黑色素瘤7例,乳腺癌6例,其它肿瘤4例。经DM-PTA化疗后2例(晚期黑色素瘤和乳腺癌肺转移各1例)达PR,2例MR,客观有效率仅3.6%,局部应用DM-PTA治疗4例胸水,其中2例胸水明显减少。不良反应以恶心呕吐为主,发生率64.1%,其中(WHO)Ⅰ+Ⅱ级占50%,Ⅲ级14.1%,由于未见其他明显器官毒性,并参照国外有关文献,后期试验在5-HT3受体阻断剂的镇吐下,6例患者接受较高剂量DM-PTA持续静脉滴注治疗(分别为2600mg/m2和3000mg/m2,连用5天),结果仍未见客观缓解,且6例患者均出现躯体局部肌肉抽搐,停药后自行缓解。结论:DTIC同类物DM-PTA虽临床前动物实验治疗取得较好的疗效,但临床缓解率低,缺乏临床应用前景。更多还原

【Abstract】 Objective: To investigate the efficacy and toxicity of dimethyl phenylatriazene(DM PTA) in the treatment of various solid tumors. Methods: The initiating dose for phase Ⅰ clinical trial was 80 mg/m2 and escalated based on Fibonaci rule. The recommanded dose of phase Ⅱ clinical study was 1 600 mg/m2 for consecutive days. Results: Thirty six patients were enrolled in phase Ⅰ clinical trial. The MTD was 2 000 mg/m2. The dose limiting toxicity was nausea/vomiting. The recommanded dose for 5 phase Ⅱ study was 1 600mg/m2 in 5 consective days every 3 weeks. Fifty nine patients with advanced cancer were enrolled into phase Ⅱ clinical trial including 25 patients with NSCLC, 5 SCLC, 7 NHL,5 HD ,7 melanoma, 6 breast carcinoma and 4 others. 2 PR (1 patient with advanced melanoma and 1 breast carcinoma with pulmonary metastasis ) and 2 MR were observed after at least 2 course of DA PTA treatment with overall response rate of 3.6%(ITT). Meanwhile improvement was observed in 2 with malignant pleural effusion following the intrapleural adminstration. Major toxicity was nausea and vomiting with no apparent organ toxicities. With the support of 5 HT3 antagonist, 6 patients were treated at higher dose (2 600-3 000mg/m2,d1-5), however, no objective response was obtained, and all of them suffered from transient locoregional muscle spasm. Conclusion: Dimethyl phenyltriazene (DM PTA), a DTIC analogue, though seemed promising in pre clinical studies, only minimal clinical response was obtained in this clinical study.更多还原