[History of photodynamic therapy--past, present and future].

Photodynamic therapy is achieved by a photodynamic reaction which is induced by excitation of photosensitizer exposed to light. This phenomenon was first reported by Raab et al in 1990. In 1960 Lipson et al reported hematoporphyrin derivative (HpD) by treating hematoporphyrin chloride with hydrochloric acid and sulfuric acid. The development of HpD established the basis of today's photodynamic therapy (PDT). Dougherty reported the treatment of skin tumors by PDT first with an argon dye laser in 1978. The author and his colleagues began basic studies of this treatment using HpD supplied by Dougherty and argon dye laser in canine lung cancer in 1978. These studies confirmed the effectiveness and safety of the method. Bronchofiberscopic PDT for early stage central type squamous cell carcinoma was performed by the authors in 1980 for the first time in the world and complete cure was obtained. Since then PDT has been attracted much attention. The photosensitizer and the laser with a specific wavelength are the key point of PDT. Photofrin, a porfimer sodium (Japan Lederle Co. Ltd., Tokyo, Japan) and excimer dye laser (Hamamatsu Photonics Co. Ltd., Hamamatsu, Japan) obtained governmental approval for clinical use in Japan in 1994, which is equivalent to FDA approval in the US. This method is now used clinically in Canada for certain indications and the Netherlands. In the US it is only approved for compassionate use in cancer of the esophagus. A total of more than 3,000 tumors in the various organs have been treated by PDT so far in 32 countries. The most frequently treated organ is the lung, with 808 cases. A phase II clinical study of PDT for early stage cancer cases of the lung, esophagus, stomach, cervix and urinary bladder was performed in 15 institutions from 1989 to early 1992. The results showed that PDT can successfully treat more than at least 50% of patients with early stage cancer cancer that would otherwise have to be treated by surgery and this means that PDT can contribute to their QOL. The cost effectiveness of PDT versus operation was estimated by the calculation based on QALY's (Quality Adjusted Life Year's saved) by Fujino of the Economics Department of Chuo University. According to this calculation PDT was estimated to be at least 30 percent less than the cost of operation. PDT is indicated in cases with superficial localized early stage lung cancer as a curative treatment and as a palliative treatment for opening stenotic or obstructed bronchi due to tumor prior to the combination therapy with surgery. Recent studies on photodynamic therapy (PDT) began just two decades ago, therefore there are still a large number of unsolved problems. However PDT will have many applications in a wide range of fields from preclinical to clinical medical science. In lung cancer, the indications will be extended for early stage lung cancer and improvement of therapeutic results will be achieved by the development of new photosensitizers such as chlorin, pheophorbide, phthalocyanin, ALA, benzoporphyrin, etc which can be excited by longer wavelength and new lasers such as pulsed excimer dye, YAG-OPO and diode lasers. Through these new developments the indications of this treatment for malignant will continue to expand.