Photodynamic Attack on Lung Cancer

When cancer patients first begin to learn about the light-based treatment approach called photodynamic therapy (PDT), they eventually pop the question: Where can I get this treatment?

The answer is much more difficult than you might think. Many clinics and hospitals that offer PDT don’t necessarily treat the full range of cancers and other diseases for which the therapy may be approved in that country. Hundreds of clinics offer PDT for non-melanoma skin cancers but not for the more dangerous or life-threatening cancers, even though the treatment is approved for many other types.

When it comes to lung cancer, the deadliest cancer worldwide, the choices seem few and far between. Based on our assessment of the offerings around the globe, Japan and the United States have the most extensive offerings for the photodynamic treatment of lung cancer. In this article, we will focus on Japan and consider a study that was recently published for the treatment of lung cancer.

Using PDT for Lung Cancer in Japan

First, a little background. Though lung cancer has been successfully treated with PDT for decades, the treatment is most effective for a type of lung cancer known as central lung cancer. This malignant disease involves the bronchi, the tubes that carry air to and from your lungs. It makes good sense that a fiber-optic laser could be passed down these tubes in order to carry out the light treatment.

About one out of every three patients with non-small-cell lung cancer also has a narrowing of the bronchi or central airways due to the cancer.  This condition is technically referred to as either airway stenosis or malignant airway obstruction. It occurs during the course of disease not only for lung cancer but also other solid tumors and metastases.

Although the usual treatment for this problem is surgery, many patients are unfit for surgery based on various criteria, such as the location and extent of the cancer. For this reason, PDT is regarded as a solid surgical alternative, and one that may result in better long-term survival as the newer photosensitizing agents and other methods are employed.

Tumors within the bronchi—referred to as endobronchial tumors—often bleed easily. PDT can be used to cut off the blood flow to the tumor and shrinking the tumor, thus making surgery easier for removing the remaining disease. Alternatively, repeated PDT sessions can be used to eliminate any residual evidence of the tumor following the initial treatment. If the tumor is quite large, PDT may be combined with radiotherapy or chemotherapy for a more optimal effect.

Early-stage lung cancer patients could be treated with either PDT or surgery, but the preference in Japan is increasingly for PDT. “Not only early stage central type lung cancer but also local advanced lung cancers which show obstruction or stenosis of central airways are approved,” says Dr. Harubumi Kato, MD, PhD, a pioneering PDT researcher at Tokyo Medical University and the first doctor worldwide to treat lung cancer with PDT.

Greater Success with a Better Photosensitizer

Since 1994, Japanese clinics have been treating early-stage lung cancer with PDT using the photosensitizing agent Photofrin, plus the Argon dye laser or Excimer dye laser. Japanese doctors also treat esophageal, gastric and cervical cancer with Photofrin-PDT. Beginning in 2003, however, the focus for lung cancer treatment shifted to using the superior chlorin-based photosensitizer called Laserphyrin (generic name: talaporfin sodium, NPe6), along with a diode laser. (See our preceding Discoveries article for more details on Laserphyrin.)

Acccording to the 2003 American College of Chest Physicians guidelines, PDT is recommended as a curative strategy for only small lesions, i.e., those less than or equal to one centimeter in diameter. But that’s based on the very limited use of Photofrin-PDT, an outdated form of the treatment. In Japan, the use of Laserphyrin-PDT is rapidly changing the entire landscape of treatment for this devastating cancer.  In the process,  it’s radically improving the way the medical profession views PDT.

Several years ago, Dr. Kato and his colleagues at Tokyo Medical University reported on a large study of Laserphyrin-PDT for central lung cancer lesions. The main findings were as follows:

• For lesions smaller than one centimeter in diameter, the complete remission rate was 94%.
• For lesions greater than one centimeter, the complete remission rate was just over 90%.
• After the mass of large tumors and deeply invasive tumors had been reduced by another ablation method (electrocautery), Laserphyrin-PDT was able to destroy the residual cancer lesions.
• Upon achieving a complete remission, and regardless of tumor size, the Laserphyrin-PDT prevented recurrences from taking place.

These findings were reported in the 1 April 2010 issue of Clinical Cancer Research. Moreover, the complete response and partial response rates together were 100% for all lesion sizes. With repeated PDT treatments, it is likely that many partial response can become complete responses.

“In early stage lung cancer of central type squamous cell carcinoma showed very good result so far,” says Dr. Kato. “Almost 100% five-year survival was obtained. My previous experience at Tokyo Medical University from 1980 to 2008 showed about 92% five-year survival among about 300 patients with early-stage lung cancer.” Dr Kato is an Emeritus Professor in the Department of Surgery and Honorary President at Tokyo Medical University and Niizashiki Central General Hospital (based in Saitama, Japan).

Hope for Advanced-Stage Lung Cancer

Patients with advanced-stage lung cancer often require palliative treatment if the airways are blocked or bleeding, either of which may result in death. PDT commonly results in the rapid return to ease of breathing and moreover has limited side effects.

In a recent study, Dr. Kato and his colleagues evaluated the safety and efficacy of PDT with chemotherapy for advanced lung cancer with airway stenosis (again, the narrowing of the central airways that, in turn, makes breathing difficult). The overall one-year survival rate was 30%, about the same as with conventional methods. However, it remains to be seen whether those patients who survive have better long-term outcomes with PDT than with the more conventional treatment methods.

For all patients, PDT reduced symptoms (such as shortness of breath) and improved the quality of life. PDT has far fewer side effects than radiotherapy, which is frequently used in these cases. There was an objective response to the photodynamic treatment, with increased opening of the bronchi and prevention of obstructive pneumonia. Moreover, the treatment appeared to be safe when combined with standard chemotherapy, as reported in the 23 October 2015 International Journal of Molecular Sciences.

The combination of PDT with chemotherapy was considered a valid way to improve the airway obstruction symptoms in these lung cancer patients. The authors of the study reasoned that “PDT attempts to control internal bronchial tumor growth, and the additional systemic chemotherapy provides certain benefits for survival with advanced lung cancer.”

At this point, Dr. Kato and his colleagues propose that further randomized clinical trials are needed to compare the ability of this combined PDT-chemo approach with other strategies. If the results are supported by additional studies, Kato and his colleagues recommend that this combined PDT-chemo approach be adopted as standard therapy.

Sources

Kimura M, Miyajima K, Kojika M, Kono T, Kato H. Photodynamic Therapy (PDT) with Chemotherapy for Advanced Lung Cancer with Airway Stenosis. Int J Mol Sci. 2015 Oct 23;16(10):25466-75. doi:

Nakajima T, Yasufuku K, Sakairi Y, Shibuya K, Yoshida S, Yoshino I. Successful treatment of lung cancer by multimodal endobronchial interventions. Respiration. 2014;88(2):144-7.

Kato H. Our experience with photodynamic diagnosis and photodynamic therapy for lung cancer. J Natl Compr Canc Netw. 2012 Oct 1;10 Suppl 2:S3-8.

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Kato H., Usuda J., Okunaka T., Furukawa K., Honda H., Sakaniwa N., Suga Y., Hirata T., Ohtani K., Inoue T., et al. Basic and clinical research on photodynamic therapy at Tokyo Medical University Hospital. Lasers Surg. Med. 2006;38:371–37

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