Conquest of an Aggressive Cancer in Japan
Since the early 1990s, the photodynamic treatment of cancer has relied mainly on a light-sensitizing agent called Photofrin. This was the first photosensitizer to be approved in many countries around the world. The agent is injected into the bloodstream, whereupon it circulates throughout the body and becomes increasingly concentrated in tumors compared to normal tissues. Upon exposure to oxygen and a specific wavelength of light, the Photofrin is activated and generates highly reactive oxygen molecules that end up destroying the tumor.
The main problem with Photofrin (generic name: porfimer sodium) is that it also leaves the patient highly sensitive to light for several weeks, forcing the person to stay indoors or away from bright lights. In addition, the wavelength of light that activates this photosensitizer is not very high, and this means poor penetration of tumors. As a consequence, only small, superficial tumors can be treated with Photofrin-PDT.
Fortunately, many other photosensitizing agents have been developed since the introduction of Photofrin. These other agents generally allow for deeper tissue penetration and thus more effective treatment. Several clinically approved second-generation photosensitizing agents have attracted a great deal of attention for the treatment of aggressive cancers. These drugs are considered far superior to Photofrin. In fact, Photofrin is widely viewed as an outdated drug even though it remains widely used in the United States and elsewhere. If Photofrin was to be subjected to clinical testing today, it would not be approved because there are so many better alternatives.
Treating A Deadly Cancer With Light
Let’s now consider one of the more promising photosensitizers, known as Laserphyrin, and its use in the photodynamic treatment of an aggressive, deadly form of liver cancer known as cholangiocarcinoma. This cancer manifests as tumors in the bile ducts, either inside or outside the liver.
Cholangiocarcinoma, or cancer of the bile ducts, can be very difficult to treat with conventional methods like surgery, radiation and chemotherapy. Surgery is often not an option due to the location of the tumor, especially when that location is inside the liver. When the tumor can be surgically removed—a relatively rare situation—the cancer still returns at least 80% of the time. Radiotherapy and chemotherapy are usually ineffective, and even the most aggressive treatment regimens appear powerless against this cancer.
Photodynamic therapy (PDT), the use of laser light to destroy tumors without damaging the surrounding normal tissues, is increasingly recognized as an effective treatment option for people diagosed with bile duct tumors. And yet, most oncologists at the top cancer centers in Europe and the United States will not inform patients of this treatment, either because it’s not officially approved or because surgery and chemotherapy are considered more practical and readily accessible treatment options. Many oncologists simply lack any training in the use of PDT.
This situation is difficult to understand given the scientific evidence. In the past few decades, PDT has been clinically applied for inoperable bile duct tumors around the world. Between 1998 and 2006, a number of European cancer centers demonstrated in controlled clinical trials that PDT was effective against inoperable bile duct tumors. The most recent studies showed few treatment-related complications, improved liver function, better quality of life, and significantly prolonged survival.
Successful Use of Laserphyrin-PDT in Japan
Though the western world has been slow to embrace the scientific evidence, PDT is fast making inroads in the East. Japan has made the greatest progress in recent years. Since the 1980s, PDT using the photosensitizer Photofrin has been a popular treatment in Japan. But because of Photofrin’s phototoxicity—that is, skin sensitivity reactions to sunlight or other bright light following treatment—real progress in the use of PDT has been relatively slow in Japan.
This situation is rapidly changing thanks to the clinically approved use of Laserphyrin-PDT for lung cancer in 2004. Many clinical studies have demonstrated the efficacy of Laserphyrin-PDT for treating tumors in the central airwars of the respiratory system—also known as central lung cancer. Nonetheless, the same cannot be said for treating cholangiocarcinoma.
Aside from a few well-documented case reports and one retrospective study, Laserphyrin-PDT has yet to be more rigorously studied as a treatment for bile duct tumors in Japan. One of the most recently reported cases was that of a 72-year-old man who underwent Laserphyrin-PDT for cholangiocarcinoma at the Nagoya City University Graduate School of Medical Sciences in Japan.
In this elderly man’s case, the cholangiocarcinoma had recurred one year after successful surgery. The bile duct had been severely blocked by the cancer, very close to the original surgical site. The Nagoya doctors first considered whether the patient should undergo surgery as a curative therapy before PDT. However, the man had already undergone extensive liver surgery for the original treatment. So much of the liver had been removed by the first operation that additional surgery would likely result in fatal liver failure.
The Nagoya medical team concluded that the patient could not undergo surgery for recurrent cholangiocarcinoma. Because surgery was considered too risky, PDT presented a much better option.
The treatment basically took place as follows: Laserphyrin was injected intravenously six hours before light treatment with a 664 nanometer semiconductor laser. This high dose of laser light (which is much higher than that of Photofrin) allows for excellent tissue penetration. The patient was then instructed to avoid sunlight for two weeks in order to prevent skin photosensitivity.
Endoscopic pictures of the bile duct after PDT revealed a dramatic improvement in the bile duct opening, with the nodular lesion entirely disappearing. No adverse side effects from the PDT were detected. The researchers concluded that PDT using Laserphyrin may be a safe alternative treatment for cholangiocarcinoma, as reported in the 15 September 2015 issue of the Japanese medical journal, Internal Medicine. (This report can be downloaded as a complete PDT file by clicking here.)
Why PDT Needs to Be Taken More Seriously
What’s so noteworthy about this case is the fact that this was a recurrent cholangiocarcinoma. Such cases tend to be highly resistant to conventional chemo and radiation treatments. Even when a complete cure is not possible, Laserphyrin-PDT can help reduce suffering and prolong life in patients with advanced cholangiocarcinoma.
In a number of anecdotal cases of advanced cholangiocarcinoma, long-term survival without recurrence has been reported following PDT. Though these cases cannot be considered definitive “proof” that PDT is the best therapy for bile duct cancer, they certainly provide hope that this treatment could become the treatment of choice, especially in inoperable cases or for those bile duct lesions that are relatively shallow in depth.
One unique feature of PDT is that it damages tumors in ways that ultimately alert the immune system to the presence of cancer, essentially making the system far more active against the disease. Thus, even when not all the bile duct tumor is immediately removed by the light treatment, the immune system is able to recognize the cancer cells and eliminate the remaining disease. This new way of thinking about how to harness the anticancer immune defenses represents the future of cancer medicine.
Sources
Nanashima A, Nagayasu T. Current status of photodynamic therapy in digestive tract carcinoma in Japan. Int J Mol Sci. 2015 Feb 4;16(2):3434-40.
Skupin-Mrugalska P, Sobotta L, Kucinska M, Murias M, Mielcarek J, Düzgüneş N. Cellular changes, molecular pathways and the immune system following photodynamic treatment. Curr Med Chem. 2014;21(35):4059-73.
Zheng Y, Yin G, Le V, Zhang A, Chen S, Liang X, Liu J. Photodynamic-therapy Activates Immune Response by disrupting Immunity Homeostasis of Tumor Cells, which Generates Vaccine for Cancer Therapy. Int J Biol Sci. 2016 Jan 1;12(1):120-32
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