Purpose: Astrocytomas are extremely resistant to currently available treatments. Cranial irradiation is a mainstay of frontline therapy, but tumor recurrence is nearly universal. Paclitaxel has shown antitumor efficacy against astrocytoma cell lines, and is a potent radiosensitizer. For these reasons, we conducted a phase I study of weekly paclitaxel and concurrent cranial irradiation in patients with newly diagnosed astrocytomas. Patients and Methods: Patients with astrocytomas were eligible for this study following initial surgery if they had a Karnofsky performance score (KPS) ≥ 60%; normal hematologic, liver, and renal function; and could give informed consent. Beginning on day 1 of treatment, patients received paclitaxel by 3- hour infusion once weekly for 6 weeks, concurrent with standard cranial irradiation. Pharmacokinetic studies were performed on 10 patients. Results: Sixty patients were enrolled; 56 were fully assessable. Forty-eight had glioblastomas (GBMs), 10 anaplastic astrocytomas (AAs), and two astrocytomas. Age ranged from 21 to 81 years (median, 55); KPS ranged from 60 to 100 (median, 70). The paclitaxel dose was escalated from 20 mg/m2 to 275 mg/m2. No clinically significant anemia or thrombocytopenia occurred. Only one patient (175 mg/m2) became neutropenic. Sensory neuropathy was dose- limiting. The maximum tolerated dose (MTD) was 250 mg/m2. Paclitaxel pharmacokinetic profiles in study patients were identical to those of previously reported patients with other solid tumors. Conclusion: The MTD of paclitaxel administered weekly for 6 weeks by 3-hour infusion is 250 mg/m2. Since patients with brain tumors often have preexisting neurologic deficits, we suggest 225 mg/m2 as the optimum dose for phase II trials in this group of patients.
ASJC Scopus subject areas
- Cancer Research