Researchers at the Perelman School of Medicine at the University of Pennsylvania in collaboration with the Roswell Park Cancer Institute have received an $8 million grant from the National Cancer Institute (NCI) to study the effects of photodynamic light therapy (PDT) in patients with malignant pleural mesothelioma, a rare, aggressive and deadly cancer that most often manifests itself in the lining of the lungs and is caused almost exclusively by exposure to asbestos. The grant will fund a clinical trial and additional studies looking at the effects of PDT on the patient's immune response, the tumor cell itself, and the blood vessels surrounding the tumor.
Approximately 3,000 new cases of mesothelioma are diagnosed each year in the U.S., with numbers expected to rise worldwide due to past uncontrolled exposure to asbestos.
"Mesothelioma is a cancer for which there is currently little to no hope for a cure," says Eli Glatstein, MD, the Principal Investigator of the program project grant and professor and vice chair of Radiation Oncology, and member of Penn's Mesothelioma and Pleural Program, one of the world's leading Centers in the research and treatment of mesothelioma. "This trial represents a major step in understanding the combination of treatment modalities that will offer patients the best hope for survival and extended remission."
The study, which expects to enroll 102 patients over four years, will administer Photofrin, a photosensitizing agent that makes cancer cells more sensitive to dying from light therapy, to trial participants 24 hours prior to surgery. Patients will undergo a radical pleurectomy, the removal of the pleura or lining of the lung along with the tumor cells contained within. They will then be randomized to two arms: half will receive PDT intraoperatively via an intense laser inserted in the chest cavity during the surgery, along with post-operative standard chemotherapy; and half who will receive only post-operative chemotherapy. Photofrin absorbs the light from the laser and produces an active form of oxygen that can destroy residual microscopic cancer cells left behind after surgery. Radical pleurectomy allows mesothelioma patients to keep their lung and is associated with better postoperative quality of life and improved survival compared with other common definitive mesothelioma surgeries.
"PDT has been a part of our treatment regimen along with a lung-sparing surgery for many years, but a randomized clinical trial such as this remains necessary to prove its efficacy," says Glatstein.
PDT is known to kill cancer cells, but researchers also seek to understand the patient's immune response, the tumor microenvironment and the blood vessels in and surrounding the tumor in three additional studies funded under the grant.
The second project will examine the process by which PDT works to destroy tumor cells and look at whether there is an agent—a drug or other therapy—that can boost its effects.
The third project will look at whether certain pathways roused during surgery may play a key role in inflammation and cell growth and thus contribute to treatment failure in any way, and whether inhibiting these pathways will improve the efficacy of intraoperative PDT.
Finally, the team will study the vasculature of the tumor in patients following PDT and evaluate any changes in the vascular environment as a result of intraoperative PDT and the potential for modulation to improve the efficacy of the treatment.
"This trial will help us understand how PDT works in the body and what we may be able to do in the future to improve the body's response to the therapy," says Glatstein.