Journal of Neuro-Oncology

, Volume 107, Issue 1, pp 155–164 | Cite as

Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab naïve, recurrent glioblastoma

  • David A. Reardon
  • Annick Desjardins
  • Katherine B. Peters
  • Sridharan Gururangan
  • John H. Sampson
  • Roger E. McLendon
  • James E. HerndonII
  • Anuradha Bulusu
  • Stevie Threatt
  • Allan H. Friedman
  • James J. Vredenburgh
  • Henry S. Friedman
Clinical Study – Patient Study

Abstract

We evaluated the efficacy of carboplatin, irinotecan, and bevacizumab among bevacizumab-naïve, recurrent glioblastoma (GBM) patients in a phase 2, open-label, single arm trial. Forty eligible patients received carboplatin (area under the plasma curve [AUC] 4 mg/ml-min) on day one, while bevacizumab (10 mg/kg) and irinotecan (340 mg/m2 for patients on CYP3A-enzyme-inducing anti-epileptics [EIAEDs] and 125 mg/m2 for patients not on EIAEDs) were administered on days 1 and 14 of every 28-day cycle. Patients were evaluated after each of the first two cycles and then after every other cycle. Treatment continued until progressive disease, unacceptable toxicity, non-compliance, or voluntary withdrawal. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary endpoints included safety and median overall survival (OS). All patients had progression after standard therapy. The median age was 51 years. Sixteen patients (40%) had a KPS of 90–100, while 27 (68%) were at first progression. The median time from original diagnosis was 11.4 months. The PFS-6 rate was 46.5% (95% CI: 30.4, 61.0%) and the median OS was 8.3 months [95% confidence interval (CI): 5.9, and 10.7 months]. Grade 4 events were primarily hematologic and included neutropenia and thrombocytopenia in 20 and 10%, respectively. The most common grade 3 events were neutropenia, thrombocytopenia, fatigue, and infection in 25, 20, 13, and 10%, respectively. Eleven patients (28%) discontinued study therapy due to toxicity and 17 patients (43%) required dose modification. One patient died due to treatment-related intestinal perforation. The addition of carboplatin and irinotecan to bevacizumab significantly increases toxicity but does not improve anti-tumor activity to that achieved historically with single-agent bevacizumab among bevacizumab-naïve, recurrent GBM patients. (ClinicalTrials.gov number NCT00953121).

Keywords

Glioblastoma Angiogenesis Bevacizumab Vascular endothelial growth factor Irinotecan Carboplatin 

Abbreviations

MG

Malignant glioma

ITT

Intent-to treat

ANC

Absolute neutrophil count

AST

Aspartate aminotransferase

CNS

Central nervous system

CR

Complete response

GBM

Glioblastoma

KPS

Karnofsky performance status

ORR

Overall response rate

OS

Overall survival

PD

Progressive disease

PFS

Progression-free survival

PR

Partial response

SD

Stable disease

VEGF

Vascular endothelial growth factor

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • David A. Reardon
    • 1
    • 2
  • Annick Desjardins
    • 3
  • Katherine B. Peters
    • 3
  • Sridharan Gururangan
    • 1
    • 2
  • John H. Sampson
    • 1
  • Roger E. McLendon
    • 4
  • James E. HerndonII
    • 5
  • Anuradha Bulusu
    • 5
  • Stevie Threatt
    • 1
  • Allan H. Friedman
    • 1
  • James J. Vredenburgh
    • 3
  • Henry S. Friedman
    • 1
    • 2
  1. 1.Departments of Surgery, The Preston Robert Tisch Brain Tumor Center at DukeDuke University Medical CenterDurhamUSA
  2. 2.Departments of Pediatrics, The Preston Robert Tisch Brain Tumor Center at DukeDuke University Medical CenterDurhamUSA
  3. 3.Departments of Medicine, The Preston Robert Tisch Brain Tumor Center at DukeDuke University Medical CenterDurhamUSA
  4. 4.Departments of Pathology, The Preston Robert Tisch Brain Tumor Center at DukeDuke University Medical CenterDurhamUSA
  5. 5.Departments of Cancer Center Biostatistics, The Preston Robert Tisch Brain Tumor Center at DukeDuke University Medical CenterDurhamUSA

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