© 2002 by Society
© 2002 by the Society forNeuro-Oncology
Phase II study of irinotecan (CPT-11) in children with high-riskmalignant brain tumors: The Duke experience
The Brain Tumor Center at Duke (C.D.T, S.G., K.B.,M.W., S.T.-U., H.S.F.) and the Divisions ofNeuro-Radiology (J.E.), Pathology (R.E.M.), and Neurosurgery (A.H.F.), Duke University Medical Center,Durham, NC 27710; and Pharmacia and Upjohn (R.B.,L.L.M.), Kalamazoo, MI 49001
2 Address correspondence and reprint requests to Sridharan Gururangan, The BrainTumor Center at Duke, Duke University Medical Center, Box 3624, Durham, NC27710.
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A phase II study of irinotecan (CPT-11) was conducted at Duke UniversityMedical Center, Durham, NC, to evaluate the activity of this agent in childrenwith high-risk malignant brain tumors. A total of 22 children were enrolled inthis study, including 13 with histologically verified recurrent malignantbrain tumors (glioblastoma multiforme [GBM] 4, anaplastic astrocytoma 1,ependymoma 5, and medulloblastoma/primitive neuroectodermal tumor 3), 5 withrecurrent diffuse pontine glioma, and 4 with newly diagnosed GBM. All patientswith recurrent tumor had prior chemotherapy and/or irradiation. Each course ofCPT-11 consisted of 125 mg/m2 per week given i.v. for 4 weeksfollowed by a 2-week rest period. Patients with recurrent tumors receivedtherapy until disease progression or unacceptable toxicity. Patients withnewly diagnosed tumors initially received 3 cycles of treatment to assesstumor response and then were allowed radiotherapy at physician's choice;patients who demonstrated a response to CPT-11 prior to radiotherapy wereallowed to continue the drug after radiation until disease progression orunacceptable toxicity. A 25% to 50% dose reduction was made for grade III-IVtoxicity. Responses were assessed after every course by gadolinium-enhancedMRI of the brain and spine. Twenty-two patients received a median of 2 coursesof CPT-11 (range, 1-16). Responses were seen in 4 of 9 patients with GBM oranaplastic astrocytoma (44%; 95% confidence interval, 11%-82%) (completeresponse in 2 patients with recurrent GBM lasting 9 months and 48+ months;partial response in one patient with a newly diagnosed midbrain GBM lasting 18months prior to radiotherapy; and partial response lasting 11 months in 1patient with recurrent anaplastic astrocytoma), 1 of 5 patients with recurrentependymoma (partial response initially followed by stable disease lasting 11months), and none of 5 patients with recurrent diffuse pontine glioma. Two of3 patients with medulloblastoma/primitive neuroectodermal tumor had stabledisease for 9 and 13 months. Toxicity was mainly myelosuppression, with 12 of22 patients (50%) suffering grade II-IV neutropenia. Seven patients requireddose reduction secondary to neutropenia. CPT-11, given in this schedule,appears to be active in children with malignant glioma, medulloblastoma, andependymoma with acceptable toxicity. Ongoing studies will demonstrate ifactivity of CPT-11 can be enhanced when combined with alkylating agents,including carmustine and temozolomide.
Received July 30, 2001; Accepted November 26, 2001
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