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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.
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Radiation Oncology

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