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Safety and efficacy of the addition of bevacizumab (BV) to temozolomide (TMZ) and radiation therapy (RT) followed by BV, TMZ, and irinotecan (CPT-11) for newly diagnosed glioblastoma multiforme (GBM).

Publication ,  Journal Article
Vredenburgh, JJ; Desjardins, A; Reardon, DA; Peters, K; Herndon, JE; Kirkpatrick, J; Gururangan, S; Bailey, L; Friedman, AH; Friedman, HS
Published in: J Clin Oncol
May 20, 2009

2015 Background: Standard GBM treatment includes TMZ and RT, and results in a median progression-free survival and median survival of 6.9 and 15.8 months, respectively. GBM have high concentrations of vascular endothelial growth factor (VEGF), higher levels are associated with poorer prognosis. BV is a humanized antibody to VEGF with activity in recurrent GBMs. This study aims to improve the survival of newly diagnosed GBM patients by incorporating an anti-angiogenic agent with RT and TMZ, and adding a topoisomerase I inhibitor, and an anti-angiogenic agent to TMZ post-RT therapy. METHODS: Patients received standard RT and TMZ at 75 mg/m(2)/day, with BV at 10 mg/kg every 14 days beginning a minimum of 28 days post-operatively. Following the completion of RT, patients received 6 cycles of BV, TMZ and CPT-11. Each cycle was 28 days. BV was given at a dose of 10 mg/kg on days 1 and 15, TMZ at 200 mg/m(2) on days 1-5 and CPT-11 on days 1 and 15 at 125 mg/m(2) for patients not on an enzyme inducing anti-epileptic drug (EIAED) and 340 mg/m(2) for patients on an EIAED. The study was designed to differentiate between a 16-month survival rate of 45% and 60% with type I and II error rates of 0.05. RESULTS: 75 patients were enrolled between 8/07 and 9/08. All the patients have completed RT; 40 patients continue to receive BV, TMZ, and CPT-11. Twenty-two patients have completed 6 cycles of BV, TMZ, and CPT-11; 17 of them had a cold PET One patient developed a CNS hemorrhage (grade 2) necessitating stopping BV. Five patients developed thrombocytopenia for which TMZ was held (grade 3, n = 1; grade 4, n = 4). There were no other ≥ grade 3 toxicities, including no wound dehiscence during RT. Twelve patients had tumor progression, and 14 stopped because of toxicity, including: 6 with fatigue; 3 with PEs; 2 with grade 4 thrombocytopenia; the patient with CNS hemorrhage, and one each with a rectal abscess and sepsis. There have been 7 deaths: 5 from tumor progression; one each from sepsis and PEs. At a median follow-up of 9 months, 81% remain alive and progression-free. CONCLUSIONS: Adding BV to TMZ and RT followed by BV, TMZ with CPT-11 is tolerable and efficacious. No significant financial relationships to disclose.

Duke Scholars

Published In

J Clin Oncol

EISSN

1527-7755

Publication Date

May 20, 2009

Volume

27

Issue

15_suppl

Start / End Page

2015

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

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Vredenburgh, J. J., Desjardins, A., Reardon, D. A., Peters, K., Herndon, J. E., Kirkpatrick, J., … Friedman, H. S. (2009). Safety and efficacy of the addition of bevacizumab (BV) to temozolomide (TMZ) and radiation therapy (RT) followed by BV, TMZ, and irinotecan (CPT-11) for newly diagnosed glioblastoma multiforme (GBM). J Clin Oncol, 27(15_suppl), 2015.
Vredenburgh, J. J., A. Desjardins, D. A. Reardon, K. Peters, J. E. Herndon, J. Kirkpatrick, S. Gururangan, L. Bailey, A. H. Friedman, and H. S. Friedman. “Safety and efficacy of the addition of bevacizumab (BV) to temozolomide (TMZ) and radiation therapy (RT) followed by BV, TMZ, and irinotecan (CPT-11) for newly diagnosed glioblastoma multiforme (GBM).J Clin Oncol 27, no. 15_suppl (May 20, 2009): 2015.
Vredenburgh JJ, Desjardins A, Reardon DA, Peters K, Herndon JE, Kirkpatrick J, Gururangan S, Bailey L, Friedman AH, Friedman HS. Safety and efficacy of the addition of bevacizumab (BV) to temozolomide (TMZ) and radiation therapy (RT) followed by BV, TMZ, and irinotecan (CPT-11) for newly diagnosed glioblastoma multiforme (GBM). J Clin Oncol. 2009 May 20;27(15_suppl):2015.

Published In

J Clin Oncol

EISSN

1527-7755

Publication Date

May 20, 2009

Volume

27

Issue

15_suppl

Start / End Page

2015

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences