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Table 2 Safety profile of antiangiogenic agents for recurrent glioblastoma.

From: Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: Analysis of single-agent and combined modality approaches

Reference, (na) Treatment
regimen
Patients
discontinuing
because of an
adverse event,
n (%)
Select grade 3 or 4
adverse events,
n (%)b
Intracranial
hemorrhage
(any grade),
n (%)
Thromboembolic
events
(any grade),
n (%)
Treatment-
related
deaths,
n (%)
Bevacizumab-containing regimens
Vredenburgh [28],
(n = 23 of 32)c
BV + irinotecan 9 (28.1) N/A 0 4 (12.5) 2 (6.3)
Vredenburgh [29],
(N = 35)
BV + irinotecan 11 (31.4) N/A 1 (2.9) 4 (11.4) N/A
Narayana [33],
(n = 37 of 61)c
BV + irinotecan or carboplatin 16 (26.2) Bone marrow toxicity, 6 (9.8) 6 (9.8) 6 (9.8) 0
Friedman [31], Cloughesy [32],
(N = 167)
BV alone (n = 84)
BV + irinotecan (n = 79)
4 (4.8)
14 (17.7)
All, 43 (51.2)
Hypertension, 9 (10.7)
Wound-healing complications, 2 (2.4)
Proteinuria, 1 (1.2)
All, 56 (70.9)
Hypertension, 3 (3.8)
Wound-healing complications, 1 (1.3)
Proteinuria, 3 (3.8)
GI perforation, 2 (2.5)
3 (3.6)
3 (3.8)
ATE, 4 (4.8)
VTE, 3 (3.6)
ATE, 3 (3.8)
VTE, 9 (11.4)
2 (2.4)
1 (1.3)
Reardon [38],
(n = 27 of 59)c
BV + etoposide 7 (11.9) Neutropenia, 14 (23.7)
Infection, 5 (8.5)
Hypertension, 2 (3.4)
CNS hemorrhage, 2 (3.4) 7 (11.9) 1 (1.7)
Kreisl [49],
(N = 48)
BV → BV + irinotecan 6 (12.5) Hypertension, 2 (4.2)
Hypophosphatemia, 2 (4.2)
Bowel perforation, 1 (2.1)
0 6 (12.5) N/A
Gutin [92],
(n = 20 of 25)c
BV + hypofractionated stereotactic irradiation 3 (12) Lymphopenia, 9 (36)
Hyponatremia, 6 (24)
Bowel perforation, 1 (4)
Wound-healing complication, 1 (4%)
GI bleeding, 1 (4%)
1 (4) N/A N/A
Aflibercept       
De Groot [53],
(n = 32 of 48)c
Aflibercept alone 12 (25) CNS ischemia, 1 (2.1)
Systemic hemorrhage, 1 (2.1)
N/A N/A N/A
Cediranib       
Batchelor [112],
(N = 31)
Cediranib alone 2 (6.5) Fatigue, 6 (19.4)
ALT, 5 (16.1)
Hypertension, 4 (12.9)
N/A 1 (3.2) 0
Cilengitide       
Reardon [50], Fink [51],
(N = 81)
Cilengitide alone (2000 mg/d [n = 40] or 500 mg/d [n = 41]) N/A Convulsion, 2 (2.5)
Lymphopenia, 7 (8.6)
Neutropenia, 1 (1.2)
1 (1.2) N/A 5 (6.2)
CT-322       
Schiff [113],
(n = 51)
CT-322 ± irinotecan 13 (25.5) Neutropenia, 4 (7.8)
Hypertension, 3 (5.9)
CNS hemorrhage, 1 (2.0) N/A 1 (2.0)
XL184       
Wen [54],
(n = 153)
XL184 (175 mg qd [n = 46] or 125 mg qd [n = 107]) 18 (11.8) Fatigue, 31 (20.3)
Hypertension, 8 (5.2)
GI perforation, 3 (2.0)
Wound-healing complications, 2 (1.3)
3 (2.0; grade 3/4) 17 (11.1) N/A
  1. Abbreviations: ALT = alanine transaminase; ATE = arterial thromboembolic event; BV = bevacizumab; CNS = central nervous system; GI = gastrointestinal; N/A = not available; VTE = venous thromboembolic event.
  2. aNumber of patients with glioblastoma, where available.
  3. bIntracranial hemorrhage and thromboembolic events are reported separately.
  4. cSafety outcomes are reported for all patients.