5-Aminolevulinic acid in intraoperative photodynamic therapy of bladder cancer (results of multicenter trial).

The results of multicenter prospective trial for efficacy of combined modality treatment: transurethral resection (TUR)+photodynamic therapy (PDT) with alasens for bladder cancer are represented in the article. Trials were organized by Research Institute of Organic Intermediates and Dyes and conducted according to clinical protocol approved by Ministry of Health of Russia, at the sites of leading Russian cancer clinical centers. The trial included 45 subjects with verified diagnosis of non-muscle-invasive bladder cancer. Patients underwent TUR of bladder with simultaneous PDT as anti-relapse treatment. Alasens was administered to patients as intravesicular instillation of 3% solution in volume of 50ml with 1.5-2h exposure (prior to TUR). TUR was performed after instillation. PDT session was conducted immediately after the completion of TUR on a single occasion by means of combined local irradiation on tumor bed with diffuse irradiation on whole urinary bladder mucosa (light dose of local irradiation - 100J/cm2, diffuse irradiation - 20J/cm2). Good tolerance of the treatment was noticed, there were no complications. Among 45 patients included in the trial, 35 (78%) completed 12 month protocol follow-up without relapse. In our study PDT with alasens after TUR reported a recurrence rate of non-muscle-invasive bladder cancer for 1st year after treatment of 22%. TUR with intraoperative PDT with 5-aminolevulinic acid may offer an alternative in the treatment of non-muscle-invasive intermediate and high-risk bladder cancer.

[Intraoperative fluorescent detection and photodynamic therapy in patients with metastatic cerebral lesions].

Brain metastases are known to have poor prognosis. In spite of using modern treatments such as microsurgical resection, radiotherapy, chemotherapy, survival of these patients remains low. Due to this fact we looked for novel methods of treatment that are able to increase the recurrence-free surgical and therefore overall survival of these patients. This paper analyzes new treatment methods used in brain tumors--fluorescent detection and photodynamic therapy with 5-aminolevulinic acid.

[The role of intraoperative photodynamic therapy in complex treatment of cerebral metastases].

Cerebral metastases are the most common brain tumors in adults and are characterized by poor prognosis. Despite application of modern methods of treatment (microsurgery, radiation therapy, chemotherapy) survival rates of these patients remain low. This fact triggers development of new therapeutic options which are able to increase recurrence-free period and consequently overall survival. The article contains review of literature dealing with photodynamic therapy which is a newly introduced technique for treatment of cerebral metastases.

Photodynamic therapy of virus-associated precancer and early stages cancer of cervix uteri.

We have analyzed the results of photodynamic therapy using light-sensitizing agent "Photogem" in 72 patients - 56 women with pre-cancerous lesions of cervix and 16 women with early cervical cancer (group 1); Photosens in 47 patients - 35 women with pre-cancerous lesions (CIN III), 12 women with non-invasive cervical cancer (carcinoma in situ) (group 2); and Alasens in 22 patients - 8 women with virus-associated pre-cancerous lesions (high-grade CIN III), 14 with virus-associated early cervical cancer (carcinoma in situ, cervical cancer 1A1) (group 3). The results were as follows: group 1 - complete regression of CIN III and non-invasive cervical cancer (carcinoma in situ) was achieved in 50 (89.2%) and 11 (68.8%) cases, significant regression was achieved in 2 cases (3.6%) and in 2 cases (12.5%), stabilization was achieved in 2 cases (3.6%) and in 2 cases (12.5%), progression was achieved in 2 cases (3.6%) and in 1 case (6.2%) accordingly. In the group of patients after PDT using Photosens complete regression of CIN III and non-invasive cervical cancer (carcinoma in situ) was achieved in 33 cases (94.2%) and in 10 cases (83.4%) cases, significant regression was achieved in 1 case (2.9%) and in 1 case (8.3%), stabilization was achieved in 1 cases (2.9%) and in 1 cases (8.3%). In the group of women after surgical treatment anti-viral efficacy was assessed. It s necessary to note that not a single relapse was observed. Anti-viral effect was registered in 49 (90.4%) cases The longest HPV-free period that we observed was 5 years. 12 women with CIN III and 4 women with carcinoma in situ became pregnant.

[Combined endolaryngeal videoendoscopic surgery and photodynamic treatment of patients with recurrent laryngeal and tracheal papillomatosis].

Two-stage combined treatment of chronic recurrent papillomatosis of the larynx and trachea has been designed and tested in P.A. Herzen Research Cancer Institute. Stage I of the treatment consisted in endolaryngeal videoendoscopic surgery with Nd:YAG-laser destruction, argon-plasma coagulation and electroresection of the papilloma; stage II - postoperative photodynamic therapy (PDT) to prevent recurrence. In 1995-2007 the treatment was given to 32 patients aged 10-66 years with recurrent papillomatosis of the airways with the disease history 5-58 years. In two thirds of the patients papillomatosis involved several parts of the larynx and trachea. Squamous cell papilloma was accompanied with dysplasia of the first-second degree in 10 (31%) patients, dysplasia of the third degree - in 4 (12,5%), cancer in situ - in 3 (9,4%) patients. Human papilloma virus (HPV) was detected by hybridization in situ in 96%. The course of the treatment resulted in a complete regression (CR) of papilloma in 25 of 32 (78%), partial regression in 7 patients. The recurrence-free interval averaged 32 months (maximal 7 years) in 14 of 25 patients with CR. HPV was eradicated in a group of patients with persistent clinical remission. A 6 to 19 month follow-up recorded papilloma recurrence in 11 patients. The recurrence-free period increased 2,5-fold. In patients with dysplasia of degree I-III and cancer in situ (n=17) CR of dysplasia and preinvasive cancer foci was achieved in 15 (88%) patients.

[Clinical fluorescent diagnosis of tumors using photosensitizer photogem]. / Klinicheskaia fliuorestsentnaia diagnostika opukholei s fotosensibilizatorom fotogemom.

During clinical trials of photodynamic therapy (PDT) the tissue fluorescence spectra under 510 nm laser excitation were recorded in 22 patients with tumors of the lungs, larynx, skin, gastric and esophageal carcinoma, and cancer of the gynecological organs before (autofluorescence) and after drug administration. A spectroscopic fluorescence detection system, developed at the General Physics Institute, Russian Academy of Sciences, was applied for tumor diagnostics. The system has been used for clinical fluorescence diagnostics with the aid of HPD-type photosensitizer Photogem (Moscow Institute of High Chemical Technologies) marked by selective retention in malignant tumors. Methods and equipment for spectra analysis aimed at estimating drug distribution in the near-surface layers of tissues, determining the tumor boundaries before photodynamic treatment, as well as studying drug pharmaco kinetics have been developed and tested. The results demonstrate the possibility of tumor detection by fluorescence even in low selectivity of drug accumulation which appears to be dependent on the stage and type of the disease and the organ involved.

[Photodynamic therapy and fluorescent diagnosis of malignant tumors using preparation photogem]. / Fotodinamicheskaia terapiia i fliuorestsentnaia diagnostika zlokachestvennykh opukholei preparatom fotogem.

From February, 1992 to May, 1993 photodynamic therapy (PDT) was applied at the State Scientific Center of Laser Medicine and the Moscow Scientific-Research Oncological Institute for the treatment of 60 patients with primary and metastatic malignant tumors of the breast, skin, respiratory and digestive organs, female reproductive organs, and urinary bladder. Forty-eight patients underwent one course of PDT, 11 patients received 2 courses, and one patient was given 3 courses. Russian-produced Photogem was used as the photosensitizer. It was infused intravenously 24, 48, or 72 hours before exposure to laser beam. The dose of Photogem ranged from 2.5 to 6.0 mg/kg. The density of laser radiation power during PDT sessions ranged from 100 to 1,600 mVt/cm2, energy exposure from 80 to 600 J/cm2, duration of irradiation from 3 to 45 minutes. After treatment the patients were studied in follow-up periods of 4 weeks to 17 months. Complete regression of the tumor verified morphologically was found in 62%, partial regression in 34%, and limited response or absence of an effect in 4% of cases. Fluorescent-diagnostic examination of patients was conducted at the Moscow Scientific-Research Oncological Institute. It demonstrated the reliability of this diagnostic method with the use of the preparation Photogem as the photosensitizer.