Phase I study of weekly outpatient paclitaxel and concurrent cranial irradiation in adults with astrocytomas

M. J. Glantz, H. Choy, C. M. Kearns, B. F. Cole, P. Mills, E. G. Zuhowski, S. Saris, C. H. Rhodes, E. Stopa, M. J. Egorin

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)600-609
Number of pages10
JournalJournal of Clinical Oncology
Volume14
Issue number2
Publication statusPublished - Feb 1996

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Glantz, M. J., Choy, H., Kearns, C. M., Cole, B. F., Mills, P., Zuhowski, E. G., ... Egorin, M. J. (1996). Phase I study of weekly outpatient paclitaxel and concurrent cranial irradiation in adults with astrocytomas. Journal of Clinical Oncology, 14(2), 600-609.