Abstract

Project 5 Patients with non-small cell lung cancer (NSCLC) and pleural spread have a median survival of 6 to 9 months which is similar to patients with distant metastatic spread. An exploratory trial of PhotofrinQmediated PDT in patients with NSCLC and pleural spread has recently demonstrated excellent local control and a median survival of 22 months. In this application, we propose to evaluate further pleural PDT for NSCLC and conduct studies that will lead to optimization of this approach.
The specific aims of this project are to 1) to perform a Phase II clinical trial of intrapleural Photofrin-mediated PDT in patients with stage 1MB NSCLC defined by pleural dissemination 2) to assess Photofrin levels and tumor oxygenation in tumor from patients with NSCLC and assess PDT-induced changes in molecular signaling pathways, 3) to optimize a murine model of NSCLC pleural carcinomatosis and characterize the molecular consequences of PDT and 4) to develop new strategies for light delivery and light production that can be translated into future clinical studies. The significance of the clinical study is, if the preliminary clinical results are confirmed, then a novel therapeutic approach would be available for a patient population which has a poor prognosis. The correlative studies of PhotofrinD uptake and hypoxia and the characterization of signaling pathway response to PDT in preclinical models and human tissues will be used in future studies to develop ways to improve the therapeutic index for pleural PDT.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA087971-08
Application #
8056470
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
8
Fiscal Year
2010
Total Cost
$158,008
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Davis 4th, Richard W; Snyder, Emma; Miller, Joann et al. (2018) Luminol Chemiluminescence Reports Photodynamic Therapy-Generated Neutrophil Activity In Vivo and Serves as a Biomarker of Therapeutic Efficacy. Photochem Photobiol :
Cramer, Gwendolyn; Simone 2nd, Charles B; Busch, Theresa M et al. (2018) Adjuvant, neoadjuvant, and definitive radiation therapy for malignant pleural mesothelioma. J Thorac Dis 10:S2565-S2573
Ong, Yi Hong; Padawer-Curry, Jonah; Finlay, Jarod C et al. (2018) Determination of optical properties, drug concentration, and tissue oxygenation in human pleural tissue before and after Photofrin-mediated photodynamic therapy. Proc SPIE Int Soc Opt Eng 10476:
Ong, Yi Hong; Kim, Michele M; Huang, Zheng et al. (2018) Reactive Oxygen Species Explicit Dosimetry (ROSED) of a Type 1 Photosensitizer. Proc SPIE Int Soc Opt Eng 10476:
Zhu, Timothy C; Kim, Michele M; Padawer, Jonah et al. (2018) Light Fluence Dosimetry in Lung-simulating Cavities. Proc SPIE Int Soc Opt Eng 10476:
Chandra, Abhishek; Wang, Luqiang; Young, Tiffany et al. (2018) Proteasome inhibitor bortezomib is a novel therapeutic agent for focal radiation-induced osteoporosis. FASEB J 32:52-62
Ong, Yi Hong; Finlay, Jarod C; Zhu, Timothy C (2018) Monte Carlo modelling of fluorescence in semi-infinite turbid media. Proc SPIE Int Soc Opt Eng 10492:
Yan, Lesan; Amirshaghaghi, Ahmad; Huang, Dennis et al. (2018) Protoporphyrin IX (PpIX)-Coated Superparamagnetic Iron Oxide Nanoparticle (SPION) Nanoclusters for Magnetic Resonance Imaging and Photodynamic Therapy. Adv Funct Mater 28:
Dimofte, Andreea; Finlay, Jarod; Ong, Yi Hong et al. (2018) A quality assurance program for clinical PDT. Proc SPIE Int Soc Opt Eng 10476:
Ahn, Peter H; Finlay, Jarod C; Gallagher-Colombo, Shannon M et al. (2018) Lesion oxygenation associates with clinical outcomes in premalignant and early stage head and neck tumors treated on a phase 1 trial of photodynamic therapy. Photodiagnosis Photodyn Ther 21:28-35

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