Интраоперационная фотодинамическая терапия рака мочевого пузыря с препаратом аласенс (результаты многоцетрового клинического исследования)

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 50 ml 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 – 100 J/cm2, diffuse irradiation – 20 J/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. The recurrence of bladder tumor was registered in 10 (22%) cases 6–12 months after TUR+PDT including 3 patients with recurrence 6 months after treatment, 3–9 months and 4–12 months. These patients underwent repeated TUR, whereafter their follow-up in the settings of the clinical trial was disposed. Thus, PDT with alasens after TUR allowed to decrease the recurrence rate of non-muscle-invasive bladder cancer for 1st year after treatment to 22% versus 40–80% for TUR as monotherapy according to literature data. The obtained results were comparable by efficiency with TUR combined with methods of adjuvant treatment for bladder tumors (the recurrence rates for 1-year follow-up after TUR+chemotherapy – 36–44%, after TUR+BCG – 20–59%). В статье представлены результаты многоцентрового проспективного клинического исследования эффективности комбинированного лечения: трансуретральной резекции (ТУР) + фотодинамической терапии (ФДТ) с препаратом аласенс рака мочевого пузыря. Исследования организованы ФГУП «ГНЦ «НИОПИК» и проведены в соответствии с клиническим протоколом, одобренным Минздравом России, на базе ведущих российских онкологических клинических центров. В исследовании приняли участие 45 паци- ентов-добровольцев с верифицированным диагнозом немышечно-инвазивного рака мочевого пузыря. Пациентам выполняли ТУР мочевого пузыря с одновременным проведением ФДТ в качестве противорецидивной терапии. Препарат аласенс вводили пациентам в виде 3%-го раствора однократной внутрипузырной инстилляцией в объеме 50 мл с продолжительностью экспозиции 1,5–2,0 часа (до проведения ТУР). После окончания инстилляции проводили ТУР. Сеанс ФДТ проводили однократно сразу после окончания ТУР путем сочетанного локального облучения ложа удаленной опухоли и диффузного облучения всей слизистой мочевого пузыря (плотность энергии локального облучения – 100 Дж/см2, диффузного облучения – 20 Дж/см2). Отмечена хорошая переносимость лечения, осложнений не зарегистрировано. Из 45 пациентов, включенных в исследование, 35 (78%) завершили 12-месячный протокольный срок наблюдения без рецидива. В 10 (22%) случаях был зарегистрирован рецидив опухоли мочевого пузыря через 6–12 месяцев после проведения ТУР+ФДТ, в том числе у 3 пациентов рецидив опухоли был зарегистрирован через 6 месяцев после проведения лечения, у 3 – через 9 месяцев и у 4 – через 12 месяцев. Этим пациентам была выполнена повтор- ная ТУР, после чего наблюдение за ними в рамках клинического исследования было завершено. Таким образом, проведение интраоперационной ФДТ с препаратом аласенс после ТУР позволило снизить частоту рецидивирования немышечно-инвазивного рака мочевого пузыря в течение 1-го года после проведения лечения до 22% по сравнению с 40–80% при применении ТУР в режиме монотерапии по данным литературы. Полученные результаты оказались сопоставимы по эффективности с ТУР в сочетании со стандартными методами адъювантной терапии опухолей мочевого пузыря (частота развития рецидива в течение 1 года наблюдения после ТУР+химиотерапии – 36–44%, после ТУР+БЦЖ – 20–59%).

Intraoperative photodynamic therapy of bladder cancer with alasens (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 50 ml 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 – 100 J/cm2, diffuse irradiation – 20 J/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. The recurrence of bladder tumor was registered in 10 (22%) cases 6–12 months after TUR+PDT including 3 patients with recurrence 6 months after treatment, 3–9 months and 4–12 months. These patients underwent repeated TUR, whereafter their follow-up in the settings of the clinical trial was disposed. Thus, PDT with alasens after TUR allowed to decrease the recurrence rate of non-muscle-invasive bladder cancer for 1st year after treatment to 22% versus 40–80% for TUR as monotherapy according to literature data. The obtained results were comparable by efficiency with TUR combined with methods of adjuvant treatment for bladder tumors (the recurrence rates for 1-year follow-up after TUR+chemotherapy – 36–44%, after TUR+BCG – 20–59%). </p