Bevacizumab (BVZ)-associated toxicities in children with recurrent central nervous system tumors treated with BVZ and irinotecan (CPT-11): A Pediatric Brain Tumor Consortium Study (PBTC-022)

Jason Fangusaro, Sridharan Gururangan, Tina Young Poussaint, Roger E. McLendon, Arzu Onar-Thomas, Katherine E. Warren, Shengjie Wu, Roger J. Packer, Anu Banerjee, Richard J. Gilbertson, Regina Jakacki, Amar Gajjar, Stewart Goldman, Ian F. Pollack, Henry S. Friedman, James M. Boyett, Larry E. Kun, Maryam Fouladi

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

BACKGROUND The incidence and spectrum of acute toxicities related to the use of bevacizumab (BVZ)-containing regimens in children are largely unknown. This report describes the adverse events in a recently completed large phase 2 trial of BVZ plus irinotecan (CPT-11) in children with recurrent central nervous system tumors. METHODS Pediatric Brain Tumor Consortium trial-022 evaluated the efficacy and toxicity of BVZ (10 mg/kg administered intravenously) as a single agent for 2 doses given 2 weeks apart and then combined with CPT-11 every 2 weeks (1 course = 4 weeks) in children with recurrent central nervous system tumors. Children were treated until they experienced progressive disease, unacceptable toxicity or completed up to a maximum of 2 years of therapy. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Patients who received at least 1 dose of BVZ were included for toxicity assessment. RESULTS Between October 2006 and June 2010, 92 patients evaluable for toxicity were enrolled and received 687 treatment courses. The most common toxicities attributable to BVZ included grade I-III hypertension (38% of patients), grade I-III fatigue (30%), grade I-II epistaxis (24%), and grade I-IV proteinuria (22%). Twenty-two patients (24%) stopped therapy due to toxicity. CONCLUSIONS The combination of BVZ and CPT-11 was fairly well-tolerated, and most severe BVZ-related toxicities were rare, self-limiting, and manageable.

Original languageEnglish (US)
Pages (from-to)4180-4187
Number of pages8
JournalCancer
Volume119
Issue number23
DOIs
StatePublished - Dec 1 2013

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irinotecan
Central Nervous System Neoplasms
Brain Neoplasms
Pediatrics
Epistaxis
National Cancer Institute (U.S.)
Bevacizumab
Proteinuria
Terminology
Fatigue

Keywords

  • bevacizumab
  • central nervous system tumors
  • clinical trials
  • pediatric
  • toxicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Bevacizumab (BVZ)-associated toxicities in children with recurrent central nervous system tumors treated with BVZ and irinotecan (CPT-11) : A Pediatric Brain Tumor Consortium Study (PBTC-022). / Fangusaro, Jason; Gururangan, Sridharan; Poussaint, Tina Young; McLendon, Roger E.; Onar-Thomas, Arzu; Warren, Katherine E.; Wu, Shengjie; Packer, Roger J.; Banerjee, Anu; Gilbertson, Richard J.; Jakacki, Regina; Gajjar, Amar; Goldman, Stewart; Pollack, Ian F.; Friedman, Henry S.; Boyett, James M.; Kun, Larry E.; Fouladi, Maryam.

In: Cancer, Vol. 119, No. 23, 01.12.2013, p. 4180-4187.

Research output: Contribution to journalArticle

Fangusaro, J, Gururangan, S, Poussaint, TY, McLendon, RE, Onar-Thomas, A, Warren, KE, Wu, S, Packer, RJ, Banerjee, A, Gilbertson, RJ, Jakacki, R, Gajjar, A, Goldman, S, Pollack, IF, Friedman, HS, Boyett, JM, Kun, LE & Fouladi, M 2013, 'Bevacizumab (BVZ)-associated toxicities in children with recurrent central nervous system tumors treated with BVZ and irinotecan (CPT-11): A Pediatric Brain Tumor Consortium Study (PBTC-022)', Cancer, vol. 119, no. 23, pp. 4180-4187. https://doi.org/10.1002/cncr.28343
Fangusaro, Jason ; Gururangan, Sridharan ; Poussaint, Tina Young ; McLendon, Roger E. ; Onar-Thomas, Arzu ; Warren, Katherine E. ; Wu, Shengjie ; Packer, Roger J. ; Banerjee, Anu ; Gilbertson, Richard J. ; Jakacki, Regina ; Gajjar, Amar ; Goldman, Stewart ; Pollack, Ian F. ; Friedman, Henry S. ; Boyett, James M. ; Kun, Larry E. ; Fouladi, Maryam. / Bevacizumab (BVZ)-associated toxicities in children with recurrent central nervous system tumors treated with BVZ and irinotecan (CPT-11) : A Pediatric Brain Tumor Consortium Study (PBTC-022). In: Cancer. 2013 ; Vol. 119, No. 23. pp. 4180-4187.
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title = "Bevacizumab (BVZ)-associated toxicities in children with recurrent central nervous system tumors treated with BVZ and irinotecan (CPT-11): A Pediatric Brain Tumor Consortium Study (PBTC-022)",
abstract = "BACKGROUND The incidence and spectrum of acute toxicities related to the use of bevacizumab (BVZ)-containing regimens in children are largely unknown. This report describes the adverse events in a recently completed large phase 2 trial of BVZ plus irinotecan (CPT-11) in children with recurrent central nervous system tumors. METHODS Pediatric Brain Tumor Consortium trial-022 evaluated the efficacy and toxicity of BVZ (10 mg/kg administered intravenously) as a single agent for 2 doses given 2 weeks apart and then combined with CPT-11 every 2 weeks (1 course = 4 weeks) in children with recurrent central nervous system tumors. Children were treated until they experienced progressive disease, unacceptable toxicity or completed up to a maximum of 2 years of therapy. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Patients who received at least 1 dose of BVZ were included for toxicity assessment. RESULTS Between October 2006 and June 2010, 92 patients evaluable for toxicity were enrolled and received 687 treatment courses. The most common toxicities attributable to BVZ included grade I-III hypertension (38{\%} of patients), grade I-III fatigue (30{\%}), grade I-II epistaxis (24{\%}), and grade I-IV proteinuria (22{\%}). Twenty-two patients (24{\%}) stopped therapy due to toxicity. CONCLUSIONS The combination of BVZ and CPT-11 was fairly well-tolerated, and most severe BVZ-related toxicities were rare, self-limiting, and manageable.",
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T1 - Bevacizumab (BVZ)-associated toxicities in children with recurrent central nervous system tumors treated with BVZ and irinotecan (CPT-11)

T2 - A Pediatric Brain Tumor Consortium Study (PBTC-022)

AU - Fangusaro, Jason

AU - Gururangan, Sridharan

AU - Poussaint, Tina Young

AU - McLendon, Roger E.

AU - Onar-Thomas, Arzu

AU - Warren, Katherine E.

AU - Wu, Shengjie

AU - Packer, Roger J.

AU - Banerjee, Anu

AU - Gilbertson, Richard J.

AU - Jakacki, Regina

AU - Gajjar, Amar

AU - Goldman, Stewart

AU - Pollack, Ian F.

AU - Friedman, Henry S.

AU - Boyett, James M.

AU - Kun, Larry E.

AU - Fouladi, Maryam

PY - 2013/12/1

Y1 - 2013/12/1

N2 - BACKGROUND The incidence and spectrum of acute toxicities related to the use of bevacizumab (BVZ)-containing regimens in children are largely unknown. This report describes the adverse events in a recently completed large phase 2 trial of BVZ plus irinotecan (CPT-11) in children with recurrent central nervous system tumors. METHODS Pediatric Brain Tumor Consortium trial-022 evaluated the efficacy and toxicity of BVZ (10 mg/kg administered intravenously) as a single agent for 2 doses given 2 weeks apart and then combined with CPT-11 every 2 weeks (1 course = 4 weeks) in children with recurrent central nervous system tumors. Children were treated until they experienced progressive disease, unacceptable toxicity or completed up to a maximum of 2 years of therapy. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Patients who received at least 1 dose of BVZ were included for toxicity assessment. RESULTS Between October 2006 and June 2010, 92 patients evaluable for toxicity were enrolled and received 687 treatment courses. The most common toxicities attributable to BVZ included grade I-III hypertension (38% of patients), grade I-III fatigue (30%), grade I-II epistaxis (24%), and grade I-IV proteinuria (22%). Twenty-two patients (24%) stopped therapy due to toxicity. CONCLUSIONS The combination of BVZ and CPT-11 was fairly well-tolerated, and most severe BVZ-related toxicities were rare, self-limiting, and manageable.

AB - BACKGROUND The incidence and spectrum of acute toxicities related to the use of bevacizumab (BVZ)-containing regimens in children are largely unknown. This report describes the adverse events in a recently completed large phase 2 trial of BVZ plus irinotecan (CPT-11) in children with recurrent central nervous system tumors. METHODS Pediatric Brain Tumor Consortium trial-022 evaluated the efficacy and toxicity of BVZ (10 mg/kg administered intravenously) as a single agent for 2 doses given 2 weeks apart and then combined with CPT-11 every 2 weeks (1 course = 4 weeks) in children with recurrent central nervous system tumors. Children were treated until they experienced progressive disease, unacceptable toxicity or completed up to a maximum of 2 years of therapy. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Patients who received at least 1 dose of BVZ were included for toxicity assessment. RESULTS Between October 2006 and June 2010, 92 patients evaluable for toxicity were enrolled and received 687 treatment courses. The most common toxicities attributable to BVZ included grade I-III hypertension (38% of patients), grade I-III fatigue (30%), grade I-II epistaxis (24%), and grade I-IV proteinuria (22%). Twenty-two patients (24%) stopped therapy due to toxicity. CONCLUSIONS The combination of BVZ and CPT-11 was fairly well-tolerated, and most severe BVZ-related toxicities were rare, self-limiting, and manageable.

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