PHASE-I STUDY OF WEEKLY OUTPATIENT PACLITAXEL AND CONCURRENT CRANIAL IRRADIATION IN ADULTS WITH ASTROCYTOMAS

Purpose: Astrocytomas are extremely resistant to currently available t reatments, 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 radiosensitiz er. For these reasons, we conducted a phase I study of weekly paclitax el and concurrent cranial irradiation in patients with newly diagnosed astrocytomas. Patients and Methods: Patients with astrocytomas were e ligible for this study following initial surgery if they had a Karnofs ky performance score (KPS) greater than or equal to 60%; normal hemato logic, liver, and renal function; and could give informed consent, Beg inning on day 1 of treatment, patients received paclitaxel by 3-hour i nfusion once weekly for 6 weeks, concurrent with standard cranial irra diation. 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 as trocytomas, Age ranged from 21 to 81 years (median, 55); KPS ranged fr om 60 to 100 (median, 70). The paclitaxel dose was escalated from 20 m g/m(2) to 275 mg/m(2). No clinically significant anemia or thrombocyto penia occurred. Only one patient (175 mg/m(2)) became neutropenic. Sen sory neuropathy was dose-limiting. The maximum tolerated dose (MTD) wa s 250 mg/m(2). Paclitaxel pharmacokinetic profiles in study patients w ere identical to those of previously reported patients with other soli d tumors. Conclusion: The MTD of paclitaxel administered weekly for 6 weeks by 3-hour infusion is 250 mg/m(2). Since patients with brain tum ors often have preexisting neurologic deficits, we suggest 225 mg/m(2) as the optimum dose for phase II trials in this group of patients. (C ) 1996 by American Society of Clinical Oncology.