Supplementary Material
Journal of Neuro-Oncology
Adverse event grading following CTCAE v3.0 underestimates hypertensive side effects in patients with
glioma under Bevacizumab
Elisabeth Bumes*, Sarah Rzonsa*, Markus Hutterer, Martin Proescholdt, Ulrich Bogdahn, Markus J.
Riemenschneider, Martin Uhl, Christina Wendl, Peter Hau
*equal contribution
Corresponding Author: Peter Hau, MD, Department of Neurology and Wilhelm-Sander NeuroOncology Unit,
University of Regensburg Medical School, Franz Josef Strauß-Allee 11, 93053 Regensburg, Germany.
Phone: 0049/941 941 0. Fax: 0049/941 941 3292.
E-Mail: peter.hau@ukr.de.
CTCAE
Grade 1
Grade 2
Version 3.0
Asymptomatic, transient (<24 hrs)
increase by >20 mmHg (diastolic) or to
>150/100 if previously WNL;
intervention not indicated
Recurrent or persistent (≥24 hrs) or
symptomatic increase by >20 mmHg
(diastolic) or to >150/100 if previously
WNL; monotherapy may be indicated
Grade 3
Requiring more than one drug or more
intensive therapy than previously
Grade 4
Life-threatening consequences (e.g.
hypertensive crisis)
Grade 5
Death
Version 4.0
Prehypertension (systolic BP 120 - 139
mmHg or diastolic BP 80 – 89 mmHg)
Stage 1 hypertension (systolic BP 140 159 mmHg or diastolic BP 90 - 99
mmHg); medical intervention
indicated; recurrent or persistent (≥24
hrs); symptomatic increase by >20
mmHg (diastolic) or to >140/90
mmHg if previously WNL;
monotherapy indicated
Stage 2 hypertension (systolic BP
≥160mmHg or diastolic BP
≥100mmHg); medical intervention
indicated; more than one drug or more
intensive therapy than previously used
indicated
Life-threatening consequences
(e.g. malignant hypertension, transient
or permanent neurologic deficit,
hypertensive crisis); urgent
intervention indicated
Death
Supplementary Table 1: Arterial Hypertension: Comparison of CTCAE v3.0 and v4.0
CTCAE, Common Terminology Criteria for Adverse Events; hrs, hours; WNL, within normal limits; BP, blood
pressure
CTC° ≥3
Hypertension
Proteinuria
Leukopenia
Neutropenia
Venous thrombembolic events
Arterial thrombembolic events
Bleeding
Wound healing disorder
BRAIN-trial
arm 1*
8.3%
0%
0%
1.3%
3.6%
2.4%
0%
2.4%
BRAIN-trial
arm 2*
1.3%
1.3%
6.3%
8.9%
8.9%
2.5%
4%
1.3%
Own data
9,5%
7.1%
7.1%
0%
2.4%
2.4%
0%
0%
* Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J,
Huang J, Zheng M, Cloughesy T (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27
(28):4733-4740. doi:JCO.2008.19.8721 [pii] 10.1200/JCO.2008.19.8721 [doi]
Supplementary Table 2: Toxicity compared to BRAIN-Trial
BRAIN-trial: arm 1: BEV 10mg/kg every two weeks, arm 2: BEV 10mg/kg + IRI 125/340mg/m² every two
weeks. Graded according to CTCAE version 3.0
BEV, Bevacizumab, IRI, Irinotecan; CTCAE, Common Terminology Criteria for Adverse Events