Weekly, outpatient paclitaxel and concurrent cranial irradiation in adults with brain tumors: Preliminary results and promising directions

In a phase I study, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was given weekly by 3-hour infusion for 6 weeks concurrent with daily cranial irradiation as initial treatment for patients with newly diagnosed astrocytic brain tumors. The primary goal of the study was to establish the maximum tolerated dose of paclitaxel when administered by this schedule. Sixty patients were entered into the study and received at least one course of therapy. Fifty-six patients completed treatment. The treatment regimen was well tolerated, with minimal hematologic toxicity. Peripheral neuropathy was dose-limiting. Median survival was 9.2 months for patients with glioblastoma multiforme and has not been reached for patients with anaplastic astrocytoma or astrocytoma. The maximum tolerated dose of paclitaxel in this study was 250 mg/m² administered weekly. However, because five of six patients receiving this dose of paclitaxel developed peripheral neuropathy, and because patients with brain tumors may adapt to a superimposed neuropathy less well than patients without pre-existing nervous system dysfunction, we propose 225 mg/m² as the recommended dose for subsequent phase II trials.