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PHOTODYNAMIC THERAPY
Photodynamic therapy, previously only used for esophogeal and lung cancer, offers new treatment options for aggressive cancers in new trials.

The next frontier in cancer treatment may have been here all along. Photodynamic therapy may not offer a cure for cancer, but its use, especially for aggressive and difficult to diagnose forms of cancer like lung cancer and mesothelioma, may prove to be a revolutionary form of treatment. While photodynamic therapy is currently only used to treat esophageal and non-small cell lung cancer, several clinical trials are now underway to test the efficacy of photodynamic therapy for treatment of other precancerous, cancerous, and benign tumors.

Photodynamic therapy uses a photosensitizer or a photosensitizing agent with light. These photosensitizers, injected into the bloodstream and absorbed by cells throughout the body, linger in cancer cells after injection, unlike with non-cancer cells. Around 24 to 72 hours after the initial dose, the photosensitizer produces a form of oxygen that kills cancerous cells in the exposed tumors. Photodynamic therapy can also shrink or destroy tumors by activating one’s immune system to attack tumor cells or by damaging the blood vessels in the tumor and thus denying the cancer from receiving nutrients. Besides providing a less toxic and physically damaging form of treatment compared to traditional types of chemotherapy and radiation, photodynamic therapy is usually an outpatient procedure, fostering a quicker recovery time and improving a patient’s physical well-being.

Although many of the studies and trials are only in their initial phases, this new wave of research continues to find positive results, suggesting a less-invasive future for cancer treatment may be closer than previously thought. We’ve rounded up an incomplete list of the numerous clinical trials recently finished or currently underway studying the benefits of photodynamic therapy in cancer treatment.


LUNG CANCER

Researchers at the University College in London recently launched a phase III randomized controlled trial with an incorporated phase II (pilot) component for therapeutic prevention of lung cancer using the photosensitizer drug Fotolon. Patients in the trial will undergo autofluorescence bronchoscopy to scan for high-grade lesions in the lung, and only patients with one or more high-grade lesions will participate in the trial. High-grade lesions are more likely to develop into cancer compared to low-grade lesions, and early detection can increase one’s chances of survival. Researchers hope to demonstrate a 20 percent or greater response in patients receiving photodynamic therapy to treat their lesions compared to patients in the control group. According to the National Library of Medicine, “The overall aim of the phase III is to show that the time period over which [high-grade lesions] progress to invasive lung cancer is significantly longer when treated with [photodynamic therapy] compared to surveillance alone.”

MESOTHELIOMA

Malignant mesothelioma is an aggressive, deadly cancer which develops due to exposure to asbestos. In November 2018, the journal Photochemistry and Photobiology reported researchers utilized a combined treatment of lung-sparing surgery and intraoperative photodynamic therapy followed by adjuvant chemotherapy with 90 patients to extend their lifespan to a median of three years compared to only eight months for patients receiving standard treatment. By developing a 3D culture model of micrometastatic mesothelioma, researchers aim to use this new treatment protocol to increase tumor cell death eventually.

PANCREATIC CANCER

A study from the Indiana University Health Center has found that photodynamic therapy for locally advanced pancreatic cancer is a “safe, technically feasible” form of treatment to increase tumor death. According to the study, “Increased volume and percentage of tumor necrosis were observed in 6 of 12 patients (50%).” However, this trial was only in its initial stages, and researchers recommend phase II studies.

BREAST CANCER

According to a study by the Cleveland Clinic, “Although 80% of [breast cancer] patients receive adjuvant chemotherapy, ~40% of those patients relapse and ultimately die” due to the development of metastatic breast cancer. Breast cancer cells primarily metastasize to the lung, liver, brain, bone, and skin, creating “significant morbidity.” A new study utilizing photodynamic therapy through the combination of two FDA-approved drugs (capecitabine and aminolevulinic acid) has produced many positive results, including “reduced proliferation” and “enhanced tumor cell death” as well as a reduced spread of metastatic cells.

BLADDER CANCER

Non-muscle invasive bladder cancer accounts for 75 percent of all bladder cancer diagnoses and has a recurrence rate of 60 to 70 percent. Effective treatment thus far has been limited, with only three drugs—Bacillus Calmette-Guérin (BCG), thiotepa, and valrubicin—approved in the last 30 years for treatment. A new study out of the University of Toronto aims to increase the opportunity for treatment of cancer using photodynamic therapy. Numerous trials have demonstrated promising results and an early response rate of 45 to 90.9 percent. Although photodynamic therapy often causes “collateral damage” to the surrounding areas when treating for bladder cancer, researchers have found delivery of approximately 90 J/cm2 of the compound TLD-1433, creates minimal side effects like mild fatigue and urinary frequency.

HEAD AND NECK CANCER

A 2017 report from the Journal of Clinical Oncology reports photodynamic therapy using redaporfin may be a beneficial treatment when standard treatments fail for advanced head and neck cancer patients. Redaporfin is a new photosensitizer designed to improve safety compared to similar options. According to the report, a “photodynamic effect was observed in all subjects” with a dose greater than or equal to 0.5 mg, and one patient achieved “complete tumor necrosis” of the treated area during their final photodynamic therapy session. This study, however, was just a first step and requires additional research into the treatment.

GLIOMAS

High-grade gliomas are fast-growing tumors of the glial cells and typically develop in the brain or the spine. According to AboutKidsHealth, about 120 to 150 kids are diagnosed with a high-grade glioma every year, and symptoms typically include headaches, nausea, vomiting, blurry vision, changes in behavior, and seizures. In a report from February 2019 in Journal of Neuro-Oncology, researchers from Mount Sinai in New York, the University of Pennsylvania, and the University Hospital of Munich recently completed clinical trials to demonstrate photodynamic therapy as a viable treatment for malignancies such as high-grade gliomas and other brain tumors. Researchers used 5-aminolevulinic acid (5-ALA), a photosensitizing precursor for photodynamic therapy of actinic keratosis, to selectively target tumors. According to the journal, additional randomized, controlled studies are needed to continue to observe its efficacy.

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