STUDIES ON THE TREATMENT AND CHARACTERISTICS OF THORACIC MALIGNANCIES

我们科已经制定了治疗和研究的方案 胸部恶性肿瘤，包括间皮瘤，转移性疾病， 肺癌和食道癌 在进行了一项I期试验后， 胸膜疾病的光疗（Ann Surg Oncol 1994; 1：28-37）和 免疫化疗（顺铂，干扰素， 他莫昔芬：CIT）治疗恶性胸膜间皮瘤（MPM）（Ann Surg Oncol 1995;2：214-220），一项III期试验正在进行中， 减积手术，术中光动力治疗，术后 CIT至最大减积手术和术后CIT。 这个程序有 自1993年7月以来，累积了46例MPM患者，预计总数 每组招募48名患者。目前， 两组之间生存率或复发时间的差异。 我们 还进行了一项第一阶段的试验， 在其他18名患者中，17名患者接受了紫杉醇治疗， 有MPM。 本研究证明了紫杉醇递送的可行性 以105 mg/m2持续输注120小时，同时 放疗 临床试验产生的基准研究 在间皮瘤的研究包括20种新细胞系的开发， 正在评估包括胰岛素在内的生长因子机制 生长因子，以及CD 44的存在，透明质酸结合 受体的 我们也在扩大调查范围 DNA病毒如SV 40和MPM致癌作用，在我们最初的 描述了60%的人类MPM样本具有T抗原的DNA。 这些研究包括分析血清中的T抗原抗体， PCR扩增人T抗原DNA羧基末端 MPM和T抗原-p53关系。 在间皮瘤的动物模型中， 本实验室报道了胸苷激酶基因 治疗使用逆转录病毒载体，这是继续使用， 腺病毒RSV-TK构建体。 通过靶向治疗延迟肿瘤发展 还描述了具有反义技术的IGF-1受体。 了18 肺转移患者，一项隔离肺I期试验 已经证明了用人重组肿瘤坏死因子灌注 这种细胞因子递送方法的可行性和安全性 高达9毫克。 干扰素、顺铂、5-FU和顺铂的新辅助治疗试验 甲酰四氢叶酸也正在进行其中的食管癌标记指数， 食管内超声的实用性和响应率正在 研究了

Our Section has developed protocols for the treatment and study of thoracic malignancies including mesothelioma, metastatic disease to the lungs, and esophageal cancer. After performing a Phase I trial of phototherapy for pleural disease (Ann Surg Oncol 1994; 1:28-37) and a Phase II trial of immunochemotherapy (cisplatin, interferon, and tamoxifen: CIT) for malignant pleural mesothelioma(MPM) (Ann Surg Oncol 1995;2:214-220), a Phase III trial has been ongoing which compares maximal debulking surgery, intraoperative photodynamic therapy, and postoperative CIT to maximal debulking surgery and postoperative CIT. This program has accumulated 46 patients with MPM since July 1993, with a projected total accrual of 48 patients per arm. At this time there are no significant differences in survival or time to recurrence between the two groups. We have also performed a Phase I trial investigating the use of radiation therapy and concurrent paclitaxel in 18 other patients, seventeen of which had MPM. This study demonstrated the feasibility of paclitaxel delivered as a 120 hour continuous infusion at 105 mg/m2 with concurrent radiotherapy. Benchwork investigations resulting from the clinical trials in mesothelioma have included the development of 20 new cell lines, which are being evaluated for growth factor mechanisms including the insulin growth factors, and the presence of CD44, the hyaluronic acid binding receptor. We are also expanding our investigations into the relationship of DNA viruses such as SV40 and MPM carcinogenesis, after our original description that 60% of our human MPM specimens had DNA for T-antigen. These investigations include analysis of sera for antibodies to T-antigen, PCR amplification of the carboxyl terminal end of T-antigen DNA from human MPM, and T-antigen-p53 relationships. In animal models of mesothelioma, our laboratory has reported on the efficacy of thymidine kinase gene therapy using retroviral vectors, and this is continuing using an adenoviral RSV-TK construct. Delayed tumor development by targeting the IGF-l receptor with antisense technology has also been described. For 18 patients with pulmonary metastases, a Phase I trial of isolated lung perfusion with human recombinant tumor necrosis factor has demonstrated the feasibility and safety of this method of cytokine delivery for doses up to 9 mg. A neoadjuvant trial of interferon, cisplatinum, 5-FU, and leucovorin is also ongoing in which labelling index of esophageal cancer, utility of endoesophageal ultrasound, and response rates are being studied.