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

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.

• Authors: Christopher D Turner, Sridharan Gururangan, James Eastwood, Krystal Bottom, Melody Watral, Rodney Beason, Roger E McLendon, Allan H Friedman, Sandra Tourt-Uhlig, Langdon L Miller, Henry S Friedman
• Journal: Neuro-oncology (Neuro Oncol) Vol. 4 Issue 2 Pg. 102-8 (04 2002) ISSN: 1522-8517 [Print] England
• PMID: 11916501 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Topoisomerase Inhibitors
• Irinotecan
• Camptothecin

Topics

• Adolescent
• Adult
• Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects, therapeutic use)
• Astrocytoma (drug therapy)
• Brain Neoplasms (drug therapy)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Child
• Child, Preschool
• Drug Administration Schedule
• Ependymoma (drug therapy)
• Female
• Glioblastoma (drug therapy)
• Glioma
• Humans
• Irinotecan
• Magnetic Resonance Imaging
• Male
• Medulloblastoma (drug therapy)
• Topoisomerase Inhibitors