Phase II study of combination taxol and estramustine phosphate in the treatment of recurrent glioblastoma multiforme

Taxol has activity in the treatment of high grade gliomas but estramustine phosphate (EMP) has not been used in this setting. In vitro data demonstrat es that EMP is cytotoxic to glioma cell lines and estramustine binding prot eins are expressed by glioma cells. The combination of Taxol and EMP is rep orted to be active in the treatment of hormone-refractory prostate cancer a nd in taxane-resistant breast and ovarian cancer. We therefore performed a phase II study to assess the activity and toxicity of this combination in h igh grade gliomas. Taxol was given at a dose of 225 mg/m(2) intravenously o ver three hours on day 1 and EMP was given at a dose of 900 mg/m(2) orally on days 1 through 3. Cycles were repeated every three weeks. Twenty patient s with recurrent glioblastoma multiforme (GBM) were enrolled: 11 male, medi an age 45 years. All patients received anti-epileptic medications and 17 (8 0%) had received prior chemotherapy. Of 18 evaluable patients, two had part ial responses (11%) and six had stable disease (33%) for a minimum of eight weeks. Treatment was well tolerated with grade 3 neutropenia occurring in only three patients. There were no other grade 3 or 4 toxicities. The media n time to progression for the cohort was only six weeks (range 3-60+ weeks) . The median overall survival was 12 weeks (range 3-60+ weeks). In conclusi on, the combination of Taxol and EMP is well tolerated and has modest activ ity in the treatment of recurrent GBM.