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Cancer

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Supplement: Irinotecan in Brain Tumors

1 May 2003

Volume 97, Issue S9

Pages 2351–2386

  1. Introduction

    1. Top of page
    2. Introduction
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      Introduction: Irinotecan in brain tumors (page 2351)

      Henry S. Friedman

      Article first published online: 17 APR 2003 | DOI: 10.1002/cncr.11303

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      Irinotecan in the treatment of glioma patients : Current and future studies of the North Central Cancer Treatment Group (pages 2352–2358)

      Jan C. Buckner, Joel M. Reid, Keith Wright, Scott H. Kaufmann, Charles Erlichman, Matthew Ames, Steve Cha, Judith R. O'Fallon, Lawrence J. Schaaf and Langdon L. Miller

      Article first published online: 17 APR 2003 | DOI: 10.1002/cncr.11304

      Patients with newly diagnosed, high-grade astrocytoma or recurrent glioma rarely are treated successfully with currently available pharmaceutical agents. For those patients with high-grade glioma, the median survival from the time of diagnosis does not appear to have improved since the late 1970s. Irinotecan appears to have promise in the treatment of glioma patients based on in vitro and in vivo preclinical models.

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      The emerging role of irinotecan (CPT-11) in the treatment of malignant glioma in brain tumors (pages 2359–2362)

      Henry S. Friedman, Stephen T. Keir and Peter J. Houghton

      Article first published online: 17 APR 2003 | DOI: 10.1002/cncr.11305

      Phase II trials confirmed the activity of irinotecan (CPT-11) in treatment of malignant glioma. Subsequent studies have shown that the combination of CPT-11 and an alkylating agent (particularly 1,3-bis[2-chloroethyl]-1-nitrosourea) generates supra-additive antitumor effects. Recent work has demonstrated that the use of CPT-11 in conjunction with temozolomide produces similar results. Current studies are aimed at exploring the role of O6-alkylguanine-DNA alkyltransferase (AGT) in reducing the benefits of treatment with CPT-11 + temozolomide and determining the gain derived from the inclusion of an AGT inhibitor in the treatment combination.

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      Combination therapy with irinotecan and protein kinase C inhibitors in malignant glioma (pages 2363–2373)

      Thomas C. Chen, Susan Su, David Fry and Leonard Liebes

      Article first published online: 17 APR 2003 | DOI: 10.1002/cncr.11307

      The topoisomerase-I inhibitor irinotecan currently is being used in Phase I/II trials for the treatment of recurrent malignant gliomas. Protein kinase C inhibitors such as high-dose tamoxifen also have been used in the treatment of malignant gliomas. In the current study, the role of protein kinase C inhibitors as chemosensitizers for irinotecan and their proposed mechanism of action were examined.

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      Effect of intrapatient dosage escalation of irinotecan on its pharmacokinetics in pediatric patients who have high-grade gliomas and receive enzyme-inducing anticonvulsant therapy (pages 2374–2380)

      Amar Gajjar, Murali M. Chintagumpala, Daniel C. Bowers, Dana Jones-Wallace, Clinton F. Stewart and Kristine R. Crews

      Article first published online: 17 APR 2003 | DOI: 10.1002/cncr.11308

      Irinotecan dosages can safely be escalated for patients with high-grade glioma who are receiving enzyme-inducing anticonvulsants. Pharmacokinetic monitoring of these patients is strongly encouraged.

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      Two studies evaluating irinotecan treatment for recurrent malignant glioma using an every-3-week regimen (pages 2381–2386)

      Timothy F. Cloughesy, Emese Filka, John Kuhn, Gillian Nelson, Fairooz Kabbinavar, Henry Friedman, Langdon L. Miller and Gary L. Elfring

      Article first published online: 17 APR 2003 | DOI: 10.1002/cncr.11306

      Two studies were performed to evaluate triweekly irinotecan (CPT-11) treatment regimens for adults with malignant glioma. In both studies, the observed CPT-11 activity was consistent with the results of previous studies. In addition, the second study demonstrated that the maximum tolerated dose (MTD) was higher than expected but still varied significantly among patients. Determination of MTD for each patient could lead to greater CPT-11 efficacy.

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