Clinical trials of photodynamic therapy of malignant brain tumors

Photodynamic therapy [PDT] is a local treatment for malignant tumors. In a phase 2 trial in patients with supratentorial gliomas treated with 2 mg/kg Photofrin i.v. and intraoperative cavitary PDT, we were able to conclude that PDT was safe in patients with either newly diagnosed or recurrent supratentorial malignant gliomas. There appears to be prolongation of survival in selected patients when an adequate light dose is used. The surgical mortality rate was less than 3%. We have initiated two randomized prospective trials - the first to determine if the addition of PDT to standard therapy [surgery, radiation and/or chemotherapy] prolongs the survival of patients with newly diagnosed malignant astrocytic tumors; and the second, to determine whether high light dose PDT [120 J/cm 2 ] is superior to low light dose PDT [40 J/cm 2 ] in patients with recurrent malignant astrocytic tumors. In the first 12 month 60 patients [36 males and 24 females] have been recruited to these phase III trials. There were 37 in the recurrent study and 23 in the newly diagnosed study. 64% of the tumors were glioblastoma and 23% malignant astrocytoma or malignant mixed glioma. In the trial of newly diagnosed tumors 12 were randomized to surgery with a mean age of 63.2 ± 4.0 [sem] and 11 to surgery plus PDT with a mean age of 53.4 ± 3.1. In recurrent glioma trial 19 were randomized to low light dose PDT [mean age 48.1 ± 2.5] and 18 to high light dose [age 46.4 ± 2.9]. An interim analysis will be undertaken at the time of 25 deaths in each of the studies. A multispectral digital camera has been developed for the purpose of fluorescence detection; we have used the device in PDT brain tumor cases. This investigation is supported in part by grant CA 43892 awarded by DHHS/NIH/NCI.