HISTOLOGIC EVIDENCE OF A RADIOSENSITIZING EFFECT OF TAXOL IN PATIENTSWITH ASTROCYTOMAS

The new anticancer agent Taxol appears to potentiate the effects of ra diation on brain tumor cell lines in vitro and was recently evaluated by our group as a radiosensitizer in a phase I study for primary brain tumors. In that study, we administered Taxol as a three-hour IV infus ion repeated every week for six weeks and gave daily cranial irradiati on concurrently for a total of 6000 rads. We reviewed the charts of th e 60 patients who participated in the study, and identified twelve pat ients who underwent a second surgery after treatment because of progre ssive symptoms and an enlarging intracranial mass on MRI. Pathological ly, each patient showed prominent radionecrosis, and other evidence of accelerated radiation changes (confluent areas of coagulative necrosi s, bizarre nuclei, marked thickening and fibrinoid changes in multiple blood vessels). These changes were noted many weeks earlier than woul d be expected after radiation therapy alone and were independent of ag e, and tumor histology. We postulate that the accelerated radiation ch anges may be due to the radiation sensitizing effects of Taxol. We als o noted a change of the pattern of tumor recurrence, compared to histo ric reports, and a dose-necrosis relationship where the resected tumor is formed completely of necrotic tissue in patients who received 150 mg/m(2) or higher dose of Taxol. These observations may be of signific ance for future study design.