Photodynamic therapy and mesothelioma

older woman holding her chest with one hand steading herself on the couch with the other

Some doctors have called PDT “elegant” because of its minimal side effects.

Photodynamic therapy (PDT) is an anti-cancer treatment that uses light energy with a light-sensitive drug to kill cancer cells. Some doctors have called it “elegant” because of its low toxicity and minimal side effects.

The process was discovered more than 100 years ago by a medical student in Germany and was first used to effectively treat skin cancers. Since then, Roswell Park Comprehensive Cancer Center has been instrumental in the modernization of PDT for treating other forms of cancer — most recently as a part of the therapy for pleural mesothelioma, a rare but aggressive form of lung cancer.

“Roswell Park is recognized as a world leader in PDT technology thanks in part to the late Dr. Thomas Dougherty, a brilliant research scientist who joined the Department of Experimental Biology here in the 1970s,” says Gal Shafirstein, DSc, MSc, BSc, Professor of Oncology and Director of PDT Clinical Research at Roswell Park.

Dr. Dougherty was celebrated as the "Father of Photodynamic Therapy." His novel contributions to the development of the light-sensitizing drug porfimer sodium led to the U.S. Food and Drug Administration approving its use in 1995 under the brand name Photofrin® for treating certain kinds of esophageal cancer. In 1998 the FDA approved porfimer sodium as part of a PDT therapy for early-stage non-small cell lung cancer.

“The first-generation light-sensitizing drug developed by Dr. Dougherty at Roswell Park met all the checkpoints for PDT success: it was non-toxic until activated, concentrated well in a tumor and, to a lesser degree, cleared normal tissue and was safely eliminated from the patient. Using this agent in PDT offered a safe treatment that can be added to standard-of-care therapies to improve treatment outcomes as reported in many clinical studies,” says Dr. Shafirstein.

“Photofrin is currently the only light-sensitizing drug approved for PDT use in the U.S. Clinical trials have shown that when used in multimodal combination with other treatments such as surgery and chemotherapy, PDT has the potential to improve the life expectancy of patients with pleural mesothelioma.”

How does PDT work?

Photodynamic therapy is most effective in treating mesothelioma that has not spread from the lungs to other parts of the body. Because it only works on areas of the body where light can reach, such as just below the skin or along the lining of internal organs, it is administered during surgery, when the chest cavity has been entered.

Before surgery, the patient is intravenously given the photosensitizing drug Photofrin, which is absorbed by both healthy and cancerous cells. The drug eventually leaves most of the healthy cells, but stays in the cancerous mesothelioma cells until it is triggered by a light source to destroy them. During surgery, after tumors are removed, the light is applied by laser beam to kill any remaining mesothelioma cells. This use of PDT is called intra-operative PDT, 

“The light used to activate the drug must be at a specific wavelength and color. Once activated, the Photofrin produces a reactive oxygen that prompts individual cancer cells to die. It may also kill the cancer cells by damaging tumor blood vessels and cutting off the supply of nutrients and reducing the chance that cells left behind will grow,” explains Dr. Shafirstein.

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PDT side effects are more tolerable than other treatments

The most common side effect of PDT is photosensitivity, which happens when some of the light-sensitive drug stays in healthy cells and interacts with bright sunlight. This may cause one or more of the following symptoms:

  • Sensitivity of the skin and eyes
  • Swollen skin
  • Sunburned or blistered skin

While patients should try to avoid direct sunlight, exposure to small amounts of ambient indoor light can speed up the recovery process, which usually lasts at least 30 says. Nausea and vomiting may also occur as a PDT side effect, but much less severely than with chemotherapy or radiation treatment.

“Photofrin is unique in that it’s a complex drug made from about 50 other drug sources. This allows it to stay in any cancer cells and solid tumors of different origins better than many immunotherapy drugs which target a specific cell mechanism,” Dr. Shafirstein says.

Moving PDT into the future

Roswell Park Comprehensive Cancer Center currently is part of an ongoing clinical study to determine the efficacy of an optical surface applicator (OSA), a handheld light source with the potential to improve accuracy and reduce the treatment time of intra-operative PDT for malignant pleural mesothelioma and non-small cell lung cancer. Developed by Dr. Shafirstein in collaboration with Sai Yendamuri, MD, FACS, FCCP, Professor of Oncology and Chair of Thoracic Surgery at Roswell Park, the device was patented by Roswell Park and has been licensed for commercial use by Lumeda, Inc.

“Investigations are ongoing into further advancements of intra-operative PDT for treating different forms of mesothelioma, and ways to make it more ‘user-friendly’ for use in combination with immunotherapy,” Dr. Shafirstein says.