RADIOIMMUNOTHERAPY OF EXTENSIVE STAGE SCLC

申请人的描述（Applicant's Description） SCLC在美国构成了一个主要和持续的公共卫生问题。 据估计，在178，100例肺癌中， 1997.尽管在戒烟方面取得了进展， 对于这种和其他形式的肺癌， 十年或更久。因此，SCLC仍将是一种主要癌症 问题. 大约三分之二的SCLC病例表现为广泛的 疾病（艾德），胸部扩散超出可行的辐射端口 或胸外转移。 尽管有固有的化疗和 这种组织学类型肺癌的放射敏感性，长期 存活（即，5年以上）非常罕见（1- 2%）， 在大多数研究中，生存期小于1年。 我们希望， 因此，为了检验高剂量赖特可以安全地 适用于ED-SCLC患者，这些患者具有持续的、可测量的 一线化疗后的疾病。 ED-SCLC非常适合 这种有前途的正交治疗方式的临床应用， 鉴于其长期生存前景黯淡， 辐射敏感性 我们将对艾德患者进行I期剂量递增试验- 已完成一线化疗且 使用放射性标记形式的 人源化抗CEA单克隆抗体（mAb），hMN-14。 由于 一种稳定的螯合剂，放射性核素，90 Y， 用于治疗。 用于成像、肿瘤靶向记录和 正常器官和肿瘤辐射吸收剂量的测定 111 In同位素将被使用，这是众所周知的密切 近似90 Y-hMN-14的药代动力学和生物分布 mAb. 将使用外周血干细胞以允许剂量 为了确定剂量限制性毒性， 这种新型高剂量赖特的最大耐受剂量和总体安全性 approach.

DESCRIPTION (Applicant's Description) SCLC constitutes a major and persistent public health problem in the US. It comprises 20-25 percent of the 178,100 lung cancers estimated in 1997. Despite progress towards smoking cessation, the benefits with respect to this and other forms of lung cancer may not accrue for another ten years or more. Hence, SCLC will remain a major cancer problem. Approximately two thirds of SCLC cases present as extensive disease (ED), with thoracic spread beyond practicable radiation ports or extra-thoracic metastasis. Despite the inherent chemo- and radiosensitivity of this histologic type of lung cancer, long-term survival (i.e., beyond 5 years) is very rare (1-2 percent) and median survival durations are less than 1 year in most studies. We wish, therefore, to test the hypothesis that high dose RAIT can be safely applied to patients with ED-SCLC, who have persistent, measurable disease after first-line chemotherapy. ED-SCLC is well suited to the clinical application of this promising, orthogonal therapeutic modality, given its dismal long-term survival prospects and its inherent radiosensitivity. We will conduct a phase I dose escalation trial for patients with ED- SCLC, who have completed first-line chemotherapy and who have persistent, measurable disease using a radiolabeled form of the humanized anti-CEA monoclonal antibody (mAb), hMN-14. Due to the availability of a stable chelating agent, the radionuclide, 90Y, will be used for therapy. For imaging, documentation of tumor targeting and determination of the radiation absorbed doses to normal organs and tumor sites, the 111In isotope will be used, which is known to closely approximate the pharmacokinetics and biodistribution of the 90Y-hMN-14 mAb. Peripheral blood stem cells will be utilized to allow for dose escalation and for determination of the dose-limiting toxicities, maximum tolerated dose and overall safety of this novel, high dose RAIT approach.