Photodynamic therapy (PDT) is an effective treatment for surface malignancies. Widespread peritoneal cancers are tumors that spread in an intracavitary manner on all of the surfaces of the abdominal cavity. There is no effective treatment for patients with peritoneal malignancies and these patients suffer considerable morbidity and this condition is uniformly lethal. PDT is theoretically an ideal treatment strategy for these patients with peritoneal carcinomatosis or sarcomatosis. A recent Phase I trial with Photofrin (PF) demonstrated benefit for some patients with ovarian carcinomatosis, gastrointestinal carcinomatosis and sarcomatosis by performing surgical debulking and intraperitoneal photodynamic therapy (IP-PDT). The principle investigator and co-investigators have initiated a Phase II trial of IP-PDT based on the maximally tolerated dose of light and PF as defined in the Phase I trial. Some patients treated on this study have shown benefit, but the majority of patients develop recurrent disease. Optimization of the therapeutic effects of PDT may improve the survival and decrease morbidity for patients with peritoneal malignancies who have no other treatment options. We propose in Specific Aim 1 to complete the Phase II trial of PDT with PF defining the response rates with this sensitizer at maximally tolerated dose and light levels. The cytokine response will be assessed and hemodynamic parameters monitored in patients undergoing PDT as contributing factors to the pathophysiology of systemic inflammatory response syndrome (SIRS).
In Specific Aim 2, Lutetium Texaphyrin and mTHPC will be evaluated as candidate sensitizers for improving the results with IP-PDT. In preclinical studies these second generation sensitizers have improved tumor selectivity which may contribute to improved outcome. The efficacy and tumor selectivity of these sensitizers will be evaluated in a preclinical murine model of IP-PDT, and the toxicity will be evaluated in the canine model of IP-PDT.
In Specific Aim 3, a Phase I and II trial of the optimal agent will be conducted. A clinical trial will always be ongoing in the form of either the current Phase II trial or a proposed Phase I trial during the entire time period of the grant. These clinical trials will provide the cornerstone for interactive studies with other investigators in this program project grant.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Subcommittee E - Prevention &Control (NCI)
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University of Pennsylvania
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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
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:

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