A. Kloc1, F. A. Durrani3, W. Bshara4, R. K. Pandey3, K. Attwood2, C. Nwogu1 1Roswell Park Comprehensive Cancer Center,Thoracic Surgery,Buffalo, NY, USA 2Roswell Park Comprehensive Cancer Center,Biostatistics & Bioinformatics,Buffalo, NY, USA 3Roswell Park Comprehensive Cancer Center,Cell Stress Biology,Buffalo, NY, USA 4Roswell Park Comprehensive Cancer Center,Pathology,Buffalo, NY, USA
Introduction: Lung cancer has the highest mortality in men and women in the United States, necessitating the development of novel treatments and improvement in current treatment techniques. Photodynamic therapy (PDT) consists of exposing a photosensitizer to a specific wavelength of light, resulting in the release of reactive oxygen species and has been used as an endoscopic technique for the palliation of lung cancer. Porfirmer Sodium (Photofrin®) is the only FDA approved photosensitizer for cancer treatment but has several disadvantages: mainly, limited depth of penetration and prolonged skin photo-toxicity. Multiple newer photosensitizers are in development, including PS785. The effectiveness of PS785 was compared to porfirmer sodium in the treatment of human lung cancer xenografts in mice
Methods: Human non-small cell lung cancer (NSCLC) xenografts were established in SCID mice and grouped into small (3-5mm) and large tumors (6-10mm). PS-785 or Photofrin® was administered intravenously and PDT was administered at 24, 48, or 72 hours post-injection. The primary endpoint will be the reduction of tumor volume and the other endpoints were the delay of tumor regrowth and Caspase-3 assays post-PDT.
Results: Small tumors (3-5mm) treated with PS-785 or Photofrin® at 24 or 48 hours were not significantly different in their ability to reach the 100% reduction of tumor volume, delay of tumor regrowth, and rate of tumor regrowth after the response ended. Photofrin® was able to achieve the 100% reduction of tumor volume in large tumors at all time points. PS785 was not able to achieve the 100% reduction of tumor volume in large tumors at any of the time points. Photofrin® and PS785 had statistically similar delay of tumor regrowth to PDT when small tumors were treated at 24 and 48 hours. Treatment of large tumors with Photofrin® at 24 hours had the greatest delay of tumor regrowth while large tumors treated with PS785 continued to grow at all time points. Caspase-3 levels were significantly greater when large and small NSCLC xenografts were treated with Photofrin® when compared to PS-785.
Conclusion: PS785 and Photofrin® were able to effectively treat NSCLC to a depth of ≤5mm. However, Photofrin® was more effective in treating NSCLC tumors to a depth of 6-10mm. Further efforts are required to produce photosensitizers that will facilitate PDT of larger tumors.
