EXPERIENCES WITH LOCAL PHOTODYNAMIC THERAPY WITH TPPS4 AND NON-COHERENT LIGHT IN CZECH REPUBLIC
Milena JIRÁSKOVÁ*, František VOSMÍK*, Miroslav LAPEŠ***, Milan JIRSA**
2nd Dept.of Dermatology*,1st Department of Med.**, 1st Faculty of Medicine, Charles University, U nemocnice 2, 128 08 Praha 2,
Institute for Radiation Oncology***, Na Truhlářce 100, 180 00 Praha 8,
Photodynamic therapy (PDT) using non-ionising light in the visible wavelength region, in combination with tumour-sensitising drugs such as different porphyrin containing substances is an example of relatively new treatment in dermatology. The method relies on the selective transfer of triplet to singlet oxygen and the generation of free radicals or radical ions mediated by the laser excitation of the sensitising drug. It has been applied in the treatment of different types of malignancies including skin tumours and some other skin diseases. The drug (mostly used Photofrin) is usually injected intravenously and is retained to a greater degree in the malignant tissue than in the normal tissue. The tumour necrosis is due to cytotoxic effects on the tumour cells and on the vessel wall endothelium in the tumour vascular system caused by the released singlet oxygen on the free radicals. But intravenously administered drugs cause transient cutaneous photosensitivity and patients must take photoprotective measures against daylight for about 6 weeks. Therefore and alternative photodynamic therapy for treatment skin malignant tumours and other skin lesions is topical intralesional application of sensitising drug.
Materials and methods
The highly fluorescent and photodynamically active substances, in our case not neurotoxic meso-tetra-para-sulfonato-phenyl-porphin (TPPS4) was as a 0.3% physiological saline solution injected or put in creme in the same concentration on the lesions. Sometimes the application into the solid nodules was not easy. The presence of sensitiser in lesions was controlled by UV light irradiation six hours later. The fluorescence of nodules could be observed by the eyes, but we used for verification reflex fluorometry too. The values of measurement you can see in tab. 1.
Tab.1. Reflex fluorometry values of
TPPS4 treated basalioma
After verification of the sensitiser presence (it means 6 hours after application) we used the incoherent light with wavelength over 600 nm (620-680 nm). The time of illumination ranged from 3 to 15 minutes and its duration depended on the lamp distance from the skin surface. The lamp was usually situated 2 cm above the surface. When the patient complained of burning sensations, we increased the distance between the lamp and the total dose of light was 130 - 300 J/cm2 in one day and one plaque. We controlled the results of the therapy every day. If the intensity of fluorescence after one week decreased, we repeated the local TPPS4 application before new irradiation. In some cases was the TPPS4 application not necessary and we could irradiate only. We try to use this therapy method for treatment of wards, basaliomas, solitary lesions of mycosis fungoides, Bowen disease and cases of malignant melanoma metastases.
We had 19 patients with basalioma, 15 patients with large mosaic warts, 2 with Bowen disease, 2 with one lesion mycosis fungoides, one with keratoacanthoma and 4 with melanoma metastases. All diagnoses except the warts were verified histologically.
Four patients (4 women) in age from 67 to 77 years with melanoma metastases in
different state of development of the disease were treated too. We injected TPPS4
in several nodules. The quantity of injected solution (at about 0.2 ml per nodule)
depended on the size of nodules. We controlled the results of the therapy every day.
Thirteen patients with basalioma answered very well to our therapy and basaliomas healed in a time period from 4 weeks to 10 month. In 3 cases the therapy was not successful. We suppose that it could be caused for the previous repeating cryotherapy which was followed by a scar formation in the affected area. The therapy of mosaic warts was without problems. Mostly in 2 months the soles were clear. Only one patient had to be treated with carbon laser (CO2 laser) for no effect of our therapy. Two patients with Bowen disease and two with mycosis fungoides answered on the therapy well. In the affected areas remained only light depigmentation after one month of the treatment. Also the keratoacanthoma healed in 3 months.
In our cases of melanoma metastases we received different answers after this therapy. In two patients with small nodules the nodules diminished to 5% and to 30% of its original volume (in 95 and 70%) after 8 weeks. The other two patients had a large dissemination of metastases with a big nodules and the treatment brought only partial improvement with necrosis and sequestration of nodules. One of them died before healing of individual nodules (the cause healing of death was emboly of a.pulmonalis as a complication of surgical therapy.
There is evidence that photodynamic therapy is effective in the treatment of cutaneous malignancies, especially in basaliomas, Bowen disease, solitaire lesions of mycosis fungoides. By the literature the opinions of malignant melanoma therapy are different. Sometimes no effect is described, what is probably caused by the pigment absorption of light in the malignant cells. We tried to use this method in four cases of melanoma metastases. In all cases we registered development of necrosis, even in the strongly pigmented nodules. The small lesions were later covered with crusts. Large necroses were present even in big nodules at the end of first week of the treatment. According to our opinion it is caused by the rather high concentration of photosensitiser in the lesions, so that even minute light doses are sufficient for induction of tumour necroses.
PDT is not sole effective treatment for tumours including malignant melanoma, but we suppose that it can enrich in some cases the other different therapies nad it can help in partial clearance of melanoma metastases. The advantage of the photodynamic therapy is that this therapy is less painful and is therefore better tolerated than cryotherapy.