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Journal of Neuro-Oncology

, Volume 95, Issue 3, pp 393–400 | Cite as

Phase II trial of temozolomide (TMZ) plus irinotecan (CPT-11) in adults with newly diagnosed glioblastoma multiforme before radiotherapy

  • Jennifer A. Quinn
  • Sara Xiaoyin Jiang
  • David A. Reardon
  • Annick Desjardins
  • James J. Vredenburgh
  • Allan H. Friedman
  • John H. Sampson
  • Roger E. McLendon
  • James E. HerndonII
  • Henry S. FriedmanEmail author
Clinical Study - Patient Study

Abstract

This phase II trial evaluated efficacy and safety of temozolomide (TMZ) in combination with irinotecan (CPT-11) before radiotherapy in patients with newly diagnosed glioblastoma multiforme (GBM). Prior to radiotherapy, patients were treated with a maximum of three 6-week cycles of TMZ and CPT-11. Patients received TMZ at a dose of 200 mg/m2/day on days 1–5 and CPT-11 on days 1, 8, 22, and 29, with a dose adjustment for enzyme-inducing antiepileptic drug use. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), safety, and tumor O6-methylguanine-DNA methyltransferase (MGMT) expression. Of the 42 patients treated, 8 (19%) patients achieved a partial response. Median PFS and median OS were 3.1 and 13.8 months, respectively. Grade 3 or 4 AEs were documented in 36% of patients, most of which were hematologic (29%). Twenty-four percent of patients had grade 3 or 4 non-hematologic AEs, with gastrointestinal AEs being the most common (12%) Two patients died, one of intracranial hemorrhage and one of treatment-related renal failure. Low MGMT expression, compared with high MGMT expression, showed no significant difference in ORR (25 vs. 8%), median PFS (14 vs. 5 months) or OS (21 vs. 15 months). Although TMZ plus CPT-11 is at least comparable in efficacy to TMZ alone, this combination appears more toxic and poorly tolerated. The lack of correlation of activity with MGMT expression is intriguing, but needs further evaluation in subsequent trials.

Keywords

Temozolomide Glioblastoma multiforme Irinotecan Radiotherapy Newly diagnosed 

Notes

Acknowledgments

This study was supported by NINDS Grant 5P50 NS20023-25, NIH SPORE Grant 5P50 CA108786-4, NIH Merit Award R37 CA 011898-38 and by funds from Pfizer Pharmaceuticals, New York, New York; S. X. Jiang was supported by NIH Grant TL1 RR024126.

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Jennifer A. Quinn
    • 1
  • Sara Xiaoyin Jiang
    • 1
  • David A. Reardon
    • 1
  • Annick Desjardins
    • 1
  • James J. Vredenburgh
    • 1
  • Allan H. Friedman
    • 1
  • John H. Sampson
    • 1
  • Roger E. McLendon
    • 2
  • James E. HerndonII
    • 3
  • Henry S. Friedman
    • 1
    Email author
  1. 1.Department of Surgery, The Preston Robert Tisch Brain Tumor CenterDuke University Medical CenterDurhamUSA
  2. 2.Department of PathologyDuke University Medical CenterDurhamUSA
  3. 3.Department of Biostatistics and BioinformaticsDuke University Medical CenterDurhamUSA

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