title: Phase I study of weekly outpatient paclitaxel and concurrent cranial irradiation in adults with astrocytomas.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Patients with astrocytomas were eligible for this study following initial surgery if they had a Karnofsky performance score (KPS) > or = 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Brown University School of Medicine, Providence, RI.
authors.forename: M J
authors.initials: MJ
authors.lastname: Glantz
authors.forename: H
authors.initials: H
authors.lastname: Choy
authors.forename: C M
authors.initials: CM
authors.lastname: Kearns
authors.forename: B F
authors.initials: BF
authors.lastname: Cole
authors.forename: P
authors.initials: P
authors.lastname: Mills
authors.forename: E G
authors.initials: EG
authors.lastname: Zuhowski
authors.forename: S
authors.initials: S
authors.lastname: Saris
authors.forename: C H
authors.initials: CH
authors.lastname: Rhodes
authors.forename: E
authors.initials: E
authors.lastname: Stopa
authors.forename: M J
authors.initials: MJ
authors.lastname: Egorin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001254:Astrocytoma / Q000532:radiotherapy / Q000628:therapy*; D001932:Brain Neoplasms / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005909:Glioblastoma / Q000628:therapy; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel