The overarching goal of project #2 is the assessment of the efficiency of porfimer sodium [Photofrin] in the photodynamic therapy of malignant brain tumors. Since brain tumors generally do not metastasize, improved local control should result in improved survival. We have shown Photofrin to have an effect on malignant glial tumors. Project #2 consists of two prospective clinical trials. The first [#1A] is a randomized controlled two arm clinical trail using Photofrin-PDT in newly diagnosed patients with malignant astrocytic tumors [malignant astrocytoma and glioblastoma multiforme] in order to determine whether the addition of Photofrin-PDT to standard surgical treatment[ surgical tumor resection, radiation therapy and chemotherapy] will result in a prolongation of the time to recurrence or progression and an increase in survival. Patients will be [after consent] stratified by treatment center and randomized to a no PDT control group or a high light dose [120 j/cm squared] PDT treatment group. The significance of differences in survival will be determined by the product limit estimate technique. The second is a randomized two arm clinical trial using Photfrin-PDT in recurrent malignant astrocytic tumors in order to ascertain the effect on survival of high light doses in comparison to low light doses. Patients will [after consent] be stratified by treatment center and randomized to a high light dose 120 j/cm squared or a low light dose [40 j/cm squared]. The significance of differences in survival will be determined by the product limit estimate technique. Also, we propose to carry out a number of ancillary measurements which will provide more fundamental information on the photosensitizer and light characteristics of human brain tumors. Photosensitizer measurement such as the uptake, photobleaching and distribution of Photofrin will be monitored, both by in vivo measurements at the time of surgery and PDT irradiation and by ex vivo analysis of tissue samples taken immediately before and after irradiation. Surgical specimens will be analyzed a) by extraction to measure the photosensitizer concentration and b) by confocal fluorescence microscopy, correlated with light microscopy, to assess the microdistribution of photosensitizer in the different tissues.
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