RADIOIMMUNOTHERAPY OF EXTENSIVE STAGE SCLC

描述(申请人的描述) 在美国，小细胞肺癌构成了一个重大而持久的公共卫生问题。 它占#年估计的178,100例肺癌的20%-25%。 1997年。尽管在戒烟方面取得了进展，但 对于这种和其他形式的肺癌，可能不会在 再过十年甚至更久。因此，小细胞肺癌仍将是主要的癌症。 有问题。大约三分之二的小细胞肺癌病例表现为广泛性 疾病(ED)，胸部扩散到实际辐射端口之外 或胸外转移。尽管有与生俱来的化疗 这种组织学类型肺癌的长期放射敏感性 存活率(即超过5年)非常罕见(1-2%)，中位数 在大多数研究中，生存时间都不到1年。我们希望， 因此，要检验大剂量辐射可以安全的假设 适用于持续、可测量的ED-SCLC患者 一线化疗后的疾病。ED-SCLC非常适合于 这一前景看好的正交治疗模式的临床应用， 鉴于其惨淡的长期生存前景和与生俱来的 对辐射敏感。 我们将为ED患者进行I期剂量递增试验- 小细胞肺癌，已完成一线化疗，并已 使用放射性标记形式的 人源化抗CEA单抗HMN-14。由于 一种稳定的螯合剂--放射性核素90Y的上市将 用于治疗。对于成像，肿瘤靶向和 正常器官和肿瘤的辐射吸收剂量测定 地点，将使用111In同位素，这是众所周知的 90Y-HMN-14的药代动力学和生物分布近似 Mab.将利用外周血干细胞来允许剂量 升级和剂量限制毒性的确定， 这种新型高剂量射线的最大耐受量和总体安全性 接近。

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.