>Photodynamic Therapy: Story of an "Orphan" Treatment

People are just beginning to learn of a way to use light to treat cancers selectively, allowing preservation of healthy tissue and avoiding surgery. It's called photodynamic therapy, or PDT. Although literally thousands of people have been treated this way, PDT is just becoming accepted among health care providers and offered to cancer patients. This is an overview of PDT with insights into how new cancer treatments are developed and accepted by the medical community.

How It Works
Photodynamic therapy takes advantage of a chemical interaction between light and a light-activated drug (photosensitizer) to start a series of chemical reactions that kill tumors. Certain physiological properties of tumor tissue cause the photosensitizer to be retained in tumors, but excreted from most healthy tissue. When laser light of a certain wavelength is shined on the tumor, the drug contained within it is converted to an active form that creates toxic molecules, killing cancer cells. Although the drug and light together are powerful, neither has any tumor-killing effect alone. Tumors usually shrink within one to two days of therapy. However, the laser light can only penetrate about one centimeter, or one-quarter inch, into tissue, so large bulky tumors often require repeated light exposure.

What's So Great About PDT?
PDT has several advantages. There are no cumulative toxic effects of PDT as with radiation or chemotherapy, so the procedure can be repeated several times if needed. PDT works on virtually all types of cancer. It is not specific to the cell type of the cancer, like chemotherapy agents or radiation. PDT is usually an outpatient procedure, so the person can go home the same day. It doesn't require general anesthesia like surgery. Even people who are too elderly or sick for surgery can have PDT because of its lower risk profile.

PDT: From Bench to Bedside
PDT was approved by the U. S. Food & Drug Administration for the treatment of late-stage esophageal cancer in 1996. Since then, two more cancer approvals have been issued, for early and late-stage lung cancer. Most recently, PDT was approved for actinic keratoses, precursors of skin cancer, and age-related macular degeneration, the leading cause of blindness in the elderly. In cancer treatment, PDT is most useful where local treatment of tumors is desired, such as in eliminating early cancer or shrinking large tumors that block important structures, like the esophagus or airways.

Work on PDT in humans began in the 1970's. Literally thousands of people were treated in clinical trials before PDT was approved by the FDA. The early scientists in this field often paid for their research out of their own pockets because grants for PDT were nearly non-existent.

Why the reluctance to accept PDT? In the 1970's, scientists were skeptical about the very idea of light penetrating human tissue. It took years of persistence to show that certain wavelengths (colors) of light could penetrate human tissue deeply enough to have an effect on cancer. The uniqueness of PDT may have been a factor as well. No one had ever used light to activate a drug. Health care providers didn't understand how light could be given in precise doses to act on the body in combination with a drug. Previously, medical lasers were strictly thermal ways of burning away unwanted tissue. The use of non-thermal light to activate and drug and initiate chemical reactions that harmed cancer tissue, but not normal tissue, was unprecedented and, frankly, many physicians simply did not understand it. At the time, the mechanics of timing the light application and using a non-thermal laser were mysterious to all but the few physicians and medical physicists who championed PDT in the early years. Also, early medical lasers were large, costly and finicky tools in the 1970's. The first laser had just been built in 1960, and operating early medical lasers took technical expertise that most clinicians did not possess.

Lastly, PDT is a local, not a systemic treatment. It can relieve symptoms like swallowing difficulty (or dysphagia) quite quickly, but it can't treat metastases or tumors that cover large areas. Physicians may prefer to administer a systemic treatment, like chemotherapy, or wide regional treatment, like radiation, instead of a local treatment like PDT. But the niche that PDT fills as a part of comprehensive cancer care is beginning to emerge. In coming years, PDT will likely occupy an important place in the treatment of both early and late cancer.

The Future of Healing With Light
After decades of research, PDT's time has come. Research funding for PDT is expanding, and acceptance and understanding by the medical community are improving. The future promises to bring better photosensitizers, cheaper light delivery devices, and many more applications for PDT.

Newer photosensitizers will be more tumor-selective than the currently approved drugs. They will cause less inflammation in the surrounding healthy tissue and pinpoint cancerous cells more accurately. Also, they will cause less skin and eye photosensitivity. (Currently, patients must protect their skin and eyes from bright light for as long as 30 days or more after therapy.) New methods of light delivery will make it possible to treat tumors deep within the body in the future. And research is underway to identify the role of PDT in treating pre-cancerous conditions of the esophagus. If PDT can cure early cancer of the esophagus, many people will be spared surgical removal of the esophagus, a procedure that requires weeks of recovery and permanently changes eating habits.

The history of PDT is not unlike the history of other groundbreaking new medical technologies. Medical practitioners are reluctant to implement poorly understood therapies that may or may not help their patients. Early research may show equivocal or even adverse outcomes as the methods are refined. Thus, both legitimate concern for the safety of patients and a lack of understanding of innovative techniques like PDT can delay the acceptance of new therapies by the medical community.

Photodynamic therapy offers a new treatment option to patients with cancer. It shows great promise for the future in effectively treating early-stage localized cancers without surgery. As PDT centers become more plentiful and acceptance of PDT expands, more people with cancer and pre-cancerous conditions will be offered this innovative treatment.

http://omlc.ogi.edu/pdt - the Oregon Medical Laser Center, a hospital-based research and treatment center for lasers in medical diagnostics and therapeutics in Portland, OR
http://cancernet.nci.nih.gov/clinpdq/therapy/Photodynamic_Therapy.html The National Cancer Institute: A clear and concise overview of PDT.
http://209.41.253.5:80/pdt@lmrf/main.htm The Laser Medical Research Foundation in Columbus, Ohio. One of the premier PDT centers in the United States.
http://health.upenn.edu/health/pf_files/penntoday/v8n1/ca_1.html The University of Pennsylvania's study of intraperitoneal (within the abdomen) ovarian cancer and PDT.
http://www.sanofi-synthelabous.com/products/photofrin/pdt_photofrin.html A list of U.S. PDT centers from Sanofi-Synthelabo, Inc. - the company that markets Photofrin® the photosensitizing drug used in lung and esophageal PDT.

Teresa T. Goodell, RN, MSN, CCRN, CS
Research Coordinator
Oregon Medical Laser Center
Providence St. Vincent Medical Center
9205 SW Barnes Rd.
Portland, Or, USA 97225
(503) 216-2040
OMLC website - http://omlc.ogi.edu/

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