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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。
Objective: To evaluate the anti-tumor activity and systemic toxicity of diallyl phthalate (DM-PTA) on common malignancies. Methods: According to the preclinical animal experimental results, the starting dose of Phase I clinical trial was 80mg / m2. According to the increasing dose of Fibonaci method until the MTD was found, the lower dose of MTD was the recommended dose of Phase II clinical trial. RESULTS: The MTD was found to be 2000 mg / m2 intravenously for 5 days and the dose limiting toxicity was nausea and vomiting. The recommended phase II clinical trial dose of 1600mg / m2 × 5 days, repeated every 3 weeks. In the phase Ⅱ clinical trial, 59 patients with advanced malignant tumors were treated, including 25 cases of non-small cell lung cancer, 5 cases of small cell lung cancer, 7 cases of non-Hodgkin’s lymphoma (NHL), 5 cases of Hodgkin’s disease (HD) 7 cases of tumor, 6 cases of breast cancer, 4 cases of other tumors. After DM-PTA chemotherapy, 2 cases (1 case of advanced melanoma and 1 case of lung metastasis of breast cancer) achieved PR, 2 cases of MR, the objective efficiency was only 3.6%. Topical application of DM-PTA in 4 cases of pleural effusion, including 2 cases of pleural effusion cut back. Adverse reactions to nausea and vomiting, the incidence of 64.1%, of which (WHO) Ⅰ + Ⅱ grade accounted for 50%, Ⅲ grade 14.1%, because no other obvious organ toxicity, and with reference to foreign literature, post-test in 5-HT3 6 patients received continuous intravenous infusion of DM-PTA at a higher dose (2600 mg / m2 and 3000 mg / m2, respectively, for 5 days), with no objective response and 6 Cases of patients with somatic local muscle twitching, self-remission after stopping. Conclusion: The DTIC congener DM-PTA has a good curative effect in preclinical animal experiments, but its clinical remission rate is low, which lacks the clinical application prospect.