A phase II study of paclitaxel in patients with recurrent malignant gliomausing different doses depending upon the concomitant use of anticonvulsants - A North American Brain Tumor Consortium report

BACKGROUND, The primary objective of the current study was to determine the response rate of paclitaxel in patients with recurrent malignant glioma by using different doses dependent on the concomitant use of anticonvulsants. Secondary objectives were to determine the time period to treatment failur e, to evaluate toxicities, and to obtain pharmacokinetic data. METHODS. Adult patients who had recurrent malignant glioma were treated wit h paclitaxel. Patients were treated at different doses depending on the con comitant use of anticonvulsants known to induce the p450 hepatic enzyme sys tem. Patients on such agents were treated at a dose of 330mg/m(2), whereas those not on these anticonvulsants were treated at a dose of 210 mg/m(2). T umor response was assessed at G-week intervals. Treatment was continued unt il documented tumor progression or unacceptable toxicity occurred, or a tot al of 12 paclitaxel infusions was completed. RESULTS, From January 1997 to June 1997, 23 patients were treated with pacl itaxel. Four patients were ineligible for the current study. Of the 19 elig ible patients, there were no responses seen. Four (21%) had stabilization o f disease. Median time to treatment failure was 1 month (95% confidence int erval [CI], 1-2 mos)and median survival was 7 months (95% CI, 6-10 mos). Th ree patients were removed from the current study because they had toxicity. Pharmacokinetic studies demonstrated that drug levels and clearance values were consistent with previously reported findings. CONCLUSION, Even though higher doses were administered to patients who had recurrent malignant glioma and who were on concomitant anticonvulsants, the re were no objective responses to paclitaxel. Time to tumor progression was 1 month. Further testing of paclitaxel at this dose schedule does not appe ar to be warranted in this patient population. (C) 2001 American Cancer Soc iety.