A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma

A North American Brain Tumor Consortium study

Michael D. Prados, Kathleen Lamborn, W. K.A. Yung, Kurt Jaeckle, H. Ian Robins, Minesh Mehta, Howard A. Fine, Patrick Y. Wen, Timothy Cloughesy, Susan Chang, M. Kelly Nicholas, David Schiff, Harry Greenberg, Larry Junck, Karen Fink, Ken Hess, John Kuhn

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

The purpose of this study was to determine the response to CPT-11 administered every three weeks to adults with progressive malignant glioma, treated with or without enzyme-inducing antiepileptic drug (EIAED) therapy, at the recommended phase 2 dose determined from a previous phase 1 study. Adult patients age 18 or older with a KPS of 60 or higher who had measurable recurrent grade III anaplastic glioma (AG) or grade IV glioblastoma multiforme (GBM) were eligible. No more than one prior chemotherapy was allowed, either as adjuvant therapy or for recurrent disease. The CPT-11 dose was 350 mg/m2 i.v. every three weeks in patients not on EIAED and 750 mg/m2 in patients on EIAED therapy. Patients with stable or responding disease could be treated until tumor progression or a total of 12 months of therapy. The primary end point of the study was to determine whether CPT-11 could significantly delay tumor progression, using the rate of six-month progression-free survival (PFS-6). The trial was sized to be able to discriminate between a 15% and 35% rate for the GBM group alone and between a 20% and 40% rate for the entire cohort. There were 51 eligible patients, including 38 GBM and 13 AG patients, enrolled. The median age was 52 and 42 years, respectively. PFS-6 for the entire cohort was 17.6%, PFS-6 was 15.7% (95% confidence interval [CI], 0.07-0.31) for the GBM patients and 23% (95% CI, 0.07-0.52) for AG patients. Toxicity for the group included diarrhea and myelosuppression. We conclude that the recommended phase 2 dose of CPT-11 for patients with or without EIAED was ineffective on this schedule, in this patient population.

Original languageEnglish (US)
Pages (from-to)189-193
Number of pages5
JournalNeuro-Oncology
Volume8
Issue number2
DOIs
StatePublished - Apr 1 2006

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irinotecan
Brain Neoplasms
Glioma
Glioblastoma
Anticonvulsants
Enzymes
Drug Therapy
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Prados, M. D., Lamborn, K., Yung, W. K. A., Jaeckle, K., Robins, H. I., Mehta, M., ... Kuhn, J. (2006). A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: A North American Brain Tumor Consortium study. Neuro-Oncology, 8(2), 189-193. https://doi.org/10.1215/15228517-2005-010
Prados, Michael D. ; Lamborn, Kathleen ; Yung, W. K.A. ; Jaeckle, Kurt ; Robins, H. Ian ; Mehta, Minesh ; Fine, Howard A. ; Wen, Patrick Y. ; Cloughesy, Timothy ; Chang, Susan ; Nicholas, M. Kelly ; Schiff, David ; Greenberg, Harry ; Junck, Larry ; Fink, Karen ; Hess, Ken ; Kuhn, John. / A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma : A North American Brain Tumor Consortium study. In: Neuro-Oncology. 2006 ; Vol. 8, No. 2. pp. 189-193.
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abstract = "The purpose of this study was to determine the response to CPT-11 administered every three weeks to adults with progressive malignant glioma, treated with or without enzyme-inducing antiepileptic drug (EIAED) therapy, at the recommended phase 2 dose determined from a previous phase 1 study. Adult patients age 18 or older with a KPS of 60 or higher who had measurable recurrent grade III anaplastic glioma (AG) or grade IV glioblastoma multiforme (GBM) were eligible. No more than one prior chemotherapy was allowed, either as adjuvant therapy or for recurrent disease. The CPT-11 dose was 350 mg/m2 i.v. every three weeks in patients not on EIAED and 750 mg/m2 in patients on EIAED therapy. Patients with stable or responding disease could be treated until tumor progression or a total of 12 months of therapy. The primary end point of the study was to determine whether CPT-11 could significantly delay tumor progression, using the rate of six-month progression-free survival (PFS-6). The trial was sized to be able to discriminate between a 15{\%} and 35{\%} rate for the GBM group alone and between a 20{\%} and 40{\%} rate for the entire cohort. There were 51 eligible patients, including 38 GBM and 13 AG patients, enrolled. The median age was 52 and 42 years, respectively. PFS-6 for the entire cohort was 17.6{\%}, PFS-6 was 15.7{\%} (95{\%} confidence interval [CI], 0.07-0.31) for the GBM patients and 23{\%} (95{\%} CI, 0.07-0.52) for AG patients. Toxicity for the group included diarrhea and myelosuppression. We conclude that the recommended phase 2 dose of CPT-11 for patients with or without EIAED was ineffective on this schedule, in this patient population.",
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Prados, MD, Lamborn, K, Yung, WKA, Jaeckle, K, Robins, HI, Mehta, M, Fine, HA, Wen, PY, Cloughesy, T, Chang, S, Nicholas, MK, Schiff, D, Greenberg, H, Junck, L, Fink, K, Hess, K & Kuhn, J 2006, 'A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: A North American Brain Tumor Consortium study', Neuro-Oncology, vol. 8, no. 2, pp. 189-193. https://doi.org/10.1215/15228517-2005-010

A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma : A North American Brain Tumor Consortium study. / Prados, Michael D.; Lamborn, Kathleen; Yung, W. K.A.; Jaeckle, Kurt; Robins, H. Ian; Mehta, Minesh; Fine, Howard A.; Wen, Patrick Y.; Cloughesy, Timothy; Chang, Susan; Nicholas, M. Kelly; Schiff, David; Greenberg, Harry; Junck, Larry; Fink, Karen; Hess, Ken; Kuhn, John.

In: Neuro-Oncology, Vol. 8, No. 2, 01.04.2006, p. 189-193.

Research output: Contribution to journalArticle

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T1 - A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma

T2 - A North American Brain Tumor Consortium study

AU - Prados, Michael D.

AU - Lamborn, Kathleen

AU - Yung, W. K.A.

AU - Jaeckle, Kurt

AU - Robins, H. Ian

AU - Mehta, Minesh

AU - Fine, Howard A.

AU - Wen, Patrick Y.

AU - Cloughesy, Timothy

AU - Chang, Susan

AU - Nicholas, M. Kelly

AU - Schiff, David

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AU - Hess, Ken

AU - Kuhn, John

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N2 - The purpose of this study was to determine the response to CPT-11 administered every three weeks to adults with progressive malignant glioma, treated with or without enzyme-inducing antiepileptic drug (EIAED) therapy, at the recommended phase 2 dose determined from a previous phase 1 study. Adult patients age 18 or older with a KPS of 60 or higher who had measurable recurrent grade III anaplastic glioma (AG) or grade IV glioblastoma multiforme (GBM) were eligible. No more than one prior chemotherapy was allowed, either as adjuvant therapy or for recurrent disease. The CPT-11 dose was 350 mg/m2 i.v. every three weeks in patients not on EIAED and 750 mg/m2 in patients on EIAED therapy. Patients with stable or responding disease could be treated until tumor progression or a total of 12 months of therapy. The primary end point of the study was to determine whether CPT-11 could significantly delay tumor progression, using the rate of six-month progression-free survival (PFS-6). The trial was sized to be able to discriminate between a 15% and 35% rate for the GBM group alone and between a 20% and 40% rate for the entire cohort. There were 51 eligible patients, including 38 GBM and 13 AG patients, enrolled. The median age was 52 and 42 years, respectively. PFS-6 for the entire cohort was 17.6%, PFS-6 was 15.7% (95% confidence interval [CI], 0.07-0.31) for the GBM patients and 23% (95% CI, 0.07-0.52) for AG patients. Toxicity for the group included diarrhea and myelosuppression. We conclude that the recommended phase 2 dose of CPT-11 for patients with or without EIAED was ineffective on this schedule, in this patient population.

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