Phase II study of irinotecan (CPT-11) in children with high-risk malignant brain tumors: the Duke experience. Other Scholarly Work

Turner, Christopher D, Gururangan, Sridharan, Eastwood, James et al. (2002). Phase II study of irinotecan (CPT-11) in children with high-risk malignant brain tumors: the Duke experience. . NEURO-ONCOLOGY, 4(2), 102-108. 10.1093/neuonc/4.2.109

cited authors

  • Turner, Christopher D; Gururangan, Sridharan; Eastwood, James; Bottom, Krystal; Watral, Melody; Beason, Rodney; McLendon, Roger E; Friedman, Allan H; Tourt-Uhlig, Sandra; Miller, Langdon L; Friedman, Henry S

authors

abstract

  • A phase II study of irinotecan (CPT-11) was conducted at Duke University Medical Center, Durham, NC, to evaluate the activity of this agent in children with high-risk malignant brain tumors. A total of 22 children were enrolled in this study, including 13 with histologically verified recurrent malignant brain tumors (glioblastoma multiforme [GBM] 4, anaplastic astrocytoma 1, ependymoma 5, and medulloblastoma/primitive neuroectodermal tumor 3), 5 with recurrent diffuse pontine glioma, and 4 with newly diagnosed GBM. All patients with recurrent tumor had prior chemotherapy and/or irradiation. Each course of CPT-11 consisted of 125 mg/m ( 2 ) per week given i.v. for 4 weeks followed by a 2-week rest period. Patients with recurrent tumors received therapy until disease progression or unacceptable toxicity. Patients with newly diagnosed tumors initially received 3 cycles of treatment to assess tumor response and then were allowed radiotherapy at physician's choice; patients who demonstrated a response to CPT-11 prior to radiotherapy were allowed to continue the drug after radiation until disease progression or unacceptable toxicity. A 25% to 50% dose reduction was made for grade III-IV toxicity. Responses were assessed after every course by gadolinium-enhanced MRI of the brain and spine. Twenty-two patients received a median of 2 courses of CPT-11 (range, 1-16). Responses were seen in 4 of 9 patients with GBM or anaplastic astrocytoma (44%; 95% confidence interval, 11%-82%) (complete response in 2 patients with recurrent GBM lasting 9 months and 48+ months; partial response in one patient with a newly diagnosed midbrain GBM lasting 18 months prior to radiotherapy; and partial response lasting 11 months in 1 patient with recurrent anaplastic astrocytoma), 1 of 5 patients with recurrent ependymoma (partial response initially followed by stable disease lasting 11 months), and none of 5 patients with recurrent diffuse pontine glioma. Two of 3 patients with medulloblastoma/primitive neuroectodermal tumor had stable disease for 9 and 13 months. Toxicity was mainly myelosuppression, with 12 of 22 patients (50%) suffering grade II-IV neutropenia. Seven patients required dose reduction secondary to neutropenia. CPT-11, given in this schedule, appears to be active in children with malignant glioma, medulloblastoma, and ependymoma with acceptable toxicity. Ongoing studies will demonstrate if activity of CPT-11 can be enhanced when combined with alkylating agents, including carmustine and temozolomide.

publication date

  • April 1, 2002

published in

keywords

  • Adolescent
  • Adult
  • Antineoplastic Agents, Phytogenic
  • Astrocytoma
  • Brain Neoplasms
  • Camptothecin
  • Child
  • Child, Preschool
  • Drug Administration Schedule
  • Ependymoma
  • Female
  • Glioblastoma
  • Glioma
  • Humans
  • Irinotecan
  • Magnetic Resonance Imaging
  • Male
  • Medulloblastoma
  • Topoisomerase Inhibitors

Digital Object Identifier (DOI)

Medium

  • Print

start page

  • 102

end page

  • 108

volume

  • 4

issue

  • 2