At Roswell Park's Photodynamic Therapy Center, multidisciplinary team focuses on specific modality

Photodynamic therapy is a targeted cancer therapy that administers a nontoxic drug that settles in tumor cells and is followed by the application of laser light to the tumor.

Once activated by the laser light, these “photosensitizing” drugs — such as porfimer sodium — destroy cancer cells but leave healthy cells unaffected.

Photodynamic therapy (PD) — developed in the 1970s by Thomas Dougherty, PhD, now chief emeritus of the Photodynamic Therapy Center at Roswell Park Cancer Institute — is used at centers around the world for treatment of lung, skin, breast, gynecological, esophageal, pleura, and head and neck cancers.

HemOnc Today spoke with Sandra Gollnick, PhD, director of the Photodynamic Therapy Center at Roswell Park Cancer Institute, about the center’s unique research efforts, the challenges it has faced and what future efforts are on the horizon.

Sandra Gollnick

Question: How did Roswell Park’s Photodynamic Therapy Center come about?

Answer: In the mid-1970s, Thomas Dougherty, PhD — who, at the time, was a chemist at Roswell Park — discovered that certain molecules he was working on, now known as photosensitizers or light-reactive drugs, reacted to light in a way that caused them to release singlet oxygen. This singlet oxygen release had the ability to kill tumor cells.

So, Tom set about developing these photosensitizers at Roswell. We now know this as the non-toxic drug Photofrin (porfimer sodium). The leadership at Roswell recognized that this was a fantastic discovery, but there was no funding available. Tom kept working on it, though, and proceeded to develop this photosensitizer for commercial and patient use.

In time, Photofrin was licensed to a major U.S. manufacturer, and a spin-off company was formed to further develop these technologies and ideas. At this time, the institute and the administration decided they needed to create a center, and they formed the Roswell Park Photodynamic Therapy Center — funded in part by royalties from companies that have bought Photofrin. Tom was the original chair, and he recruited a team of physicists, engineers, biologists, immunologists and chemists.

Photofrin became the first photosensitizer approved by the FDA in the 1990s and is the first photosensitizer used for the treatment of cancer. A program project grant was submitted to the NCI requesting funds to support subsequent research into PDT to further its clinical ability and to help us learn the mechanisms by which this therapy works so that we can hone it to a better therapy. This grant was awarded and was just renewed again for its 21st year of funding, making it one of the longest-funded projects at the NCI.

Q: Can you describe the need for this initiative, as well as its mission?

A: There are many anti-cancer modalities out there — radiation, surgery and chemotherapy — all of which are effective, but each of which has its own problems, in particular the damage caused to normal tissue. PDT has the ability to spare normal tissue because of its selectivity, and the selectivity comes from the fact that the photosensitizer is administered either topically or through IV.

The photosensitizer itself is rather innocuous, unless you shine light of a particular wavelength on the area. There are some side effects associated with first-generation Photofrin. There is some skin phototoxicity, and patients treated with this have to pretty much stay out of direct light for at least 6 weeks or they develop a sunburn. Essentially the patient has to wear long sleeves and a hat. It is not pleasant for the patient, but they are not living in total darkness for 6 weeks. This treatment does not place them at risk for developing melanoma.

We have subsequently developed a second-generation photosensitizer that is currently under trial here at Roswell. Also, several other places around the world have developed second-generation photosensitizers.

So, why do we need this therapy? The first disease site that PDT was approved for was late-stage NSCLC. Patients with lung cancer undergo surgery to remove the cancer, but we can only remove so much of the lung surgically. PDT was an alternative for these patients without having to remove the lobe of the lung. Our current trials of PDT are in head and neck cancer, and we have shown that this therapy can do as well of a job with minimal side effects as other treatment modalities. We need this modality to improve patients’ quality of life and the sparing of normal tissue.

Q: What makes this different from other research efforts?

A: Our ultimate goal is to improve the quality of life of our patients, and the center encompasses a multifaceted effort. Cancer is a complicated disease, and successful treatment requires expertise in numerous arenas. Members of the PDT center have expertise in tumor biology, vascular biology, immunology and pharmacology. Working together allows us to attack cancer on multiple fronts. In addition, PDT is a biophysical therapy that requires an understanding of tissue optics. For that reason, our center also includes physicists and engineers, who are critical to our development of PDT methods.

Q: Which malignancies are the primary areas of focus, and why were they chosen?

A: Historically, the initial focus has been on lung cancer because there was such a desperate need for patients with late-stage lung cancer. Repeat surgeries are not possible in these patients, and most are just not strong enough to endure chemotherapy. Skin cancer is another focus in which PDT is used quite a lot, specifically for non-melanomas. Another area PDT has been used for to some degree is in cutaneous T-cell lymphoma. Our current focus for PDT is in head and neck cancers.

Q: Can you talk about some of the key findings so far?

A: Roswell has been on the forefront of this therapy for the last 30 or so years. Most centers outside of Roswell that perform PDT have received training at Roswell, and PDT is widely used in Europe and Asia, where they have large centers themselves.

The recent key findings that we at Roswell have developed include the treatment regimens that allow PDT to be done in as minimally invasive and minimally painful a way as possible for the patient. Another key finding that we discovered is that different patient tumors have different affinities for photosensitizers. Tom Dougherty developed one type of photosensitizer, but numerous others have been developed since. Another Roswell faculty member and member of the PDT Center, Ravindra Pandey, PhD, developed numerous photosensitizers, and he has shown that they can be used in a see-and-treat manner. The photosensitizer will target to the tumor — and because the photosensitizer is fluorescent under light — you can then see the tumor and change the wavelength of the light to treat the tumor. Dr. Pandey has been successfully using this in clinical trials for the treatment of glioblastomas. Another key finding that we have discovered is that we were the first to show that when you do PDT, you induce a systemic immune response, which can inhibit distant disease. This idea has been taken further as an adjuvant therapy in mesothelioma patients who are littered with small tumors everywhere.

Q: What challenges have you faced in the early stages of this initiative, and how have you been able to overcome them?

A: For many decades and even now, there is one major challenge of PDT. That is, it’s considered a niche therapy, much like acupuncture. We at Roswell have dedicated ourselves to rigorous research to show that the mechanisms are really analogous to radiation therapy, just with light instead of X-ray. This has been our biggest challenge, and we continue to work on overcoming this by conducting the best research that we can.

Q: How do you see the center evolving/expanding in the near future?

A: One of the things we are doing at Roswell is that we are conducting the first-ever multicenter randomized trial of PDT for head and neck cancer, where we are going head-to-head against the standard of care. These centers include Roswell Park, the University of Minnesota, the University of Rochester and Johns Hopkins. Our goal is to show that PDT is not a niche therapy in the U.S. Now, outside of the U.S., PDT is a widely accepted treatment in these patients. I think the reason for this is that in Asia they have had such great success in treating bladder cancer and head and neck tumors on some level. Also, PDT is relatively cheap when compared with chemotherapy. For Europe, they have always been more open to different types of therapies and moving things along fast if they work.

Q: What type of impact can a center like this have on the effort to diagnose, treat and potentially cure certain cancers?

A: At a center like ours, which is focused on a specific therapy and where we have tremendous support and a multidisciplinary team, we have the ability to move the therapy forward more quickly because all of the tools we need are in-house. I think this is the advantage we have at the center over individual investigators around the country. – by Jennifer Southall

For more information:

Sandra Gollnick, PhD can be reached at Roswell Park Cancer Institute, Elm and Carlton streets, Buffalo, NY, 14263; email: sandra.gollnick@roswellpark.org.

Disclosure: Gollnick reports a consultant role with Cleveland BioLabs Inc.