Project 5Patients with non-small cell lung cancer (NSCLC) and pleural spread have a median survival of 6 to 9months which is similar to patients with distant metastatic spread. An exploratory trial of PhotofrinQmediatedPDT in patients with NSCLC and pleural spread has recently demonstrated excellent local controland a median survival of 22 months. In this application, we propose to evaluate further pleural PDT forNSCLC and conduct studies that will lead to optimization of this approach.
The specific aims of this projectare to 1) to perform a Phase II clinical trial of intrapleural Photofrin-mediated PDT in patients with stage 1MBNSCLC defined by pleural dissemination 2) to assess Photofrin levels and tumor oxygenation in tumor frompatients with NSCLC and assess PDT-induced changes in molecular signaling pathways, 3) to optimize amurine model of NSCLC pleural carcinomatosis and characterize the molecular consequences of PDT and4) to develop new strategies for light delivery and light production that can be translated into future clinicalstudies. The significance of the clinical study is, if the preliminary clinical results are confirmed, then a noveltherapeutic approach would be available for a patient population which has a poor prognosis. Thecorrelative studies of PhotofrinD uptake and hypoxia and the characterization of signaling pathway responseto PDT in preclinical models and human tissues will be used in future studies to develop ways to improve thetherapeutic index for pleural PDT.
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