Table 3 Toxicity of bevacizumab plus irinotecan for patients with recurrent malignant glioma

Chen [15]

Vredenburgh [16]

Thromboembolic complications (n = 4), Grade II proteinuria (n = 2), Grade II fatigue and withdrew consent(n = 4), Grade III or worse gastrointestinal toxicity (n = 4), Sepsis (n = 1), central nervous system hemorrhage (n = 1), leg ulcers (n = 1)

Bokstein [17]

Grade I hypertension (n = 1), Grade I rash (n = 1), Grade I and III fatigue (n = 3), Grade II epistaxis (n = 1), Grade II anemia (n = 1), Grade II diarrhea (n = 2), Grade II seizures (n = 1), Grade III paranoid psychosis (n = 1)

Guiu [18]

Intratumoral hemorrhage (n = 5, with spontaneous regression in 3) and thromboembolic complications including venous thrombophlebitis (n = 4), pulmonary embolism (n = 2), and myocardial infarction (n = 1); Grade III-IV hepatotoxicity (n = 2), reversible leukoencephalopathy (n = 1).

Ali [19]

Intracranial bleeding (n = 2), deep venous thrombosis (n = 1)

Desjardins [20]

Dose reduction due to gastrointestinal toxicity or neutropenia (n = 5), withdrew consent due to fatigue or gastrointestinal toxicity (n = 4), central nervous system hemorrhage (n = 1), thrombotic thrombocytopenic purpura (n = 1)

Kang [21]

Thromboembolic complications (n = 5), hemorrhage (n = 3), hematuria (n = 1), infection (n = 1), fatigue (n = 1), cough (n = 1), failure to thrive (n = 1)

Poulsen [22]

Grade III cerebral hemorrhage (n = 1), cardiac arrhythmia (atrial fibrillation), intestinal perforation (n = 1), superficial venous thrombosis (n = 1), hypertension (n = 3), neutropenia (n = 1), infection (n = 2), proteinuria (n = 1); Grade V diarrhea (n = 1)

Zuniga cohort A [23]

Grade II-III hypertension (n = 13), Grade I-II bleeding (n = 9)

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Zuniga cohort B [23]

Grade III proteinuria-renal failure (n = 1), gastrointestinal perforation (n = 1), severe nausea/vomiting (n = 4)

Friedman [24]

Hypertension (n = 21; Grade≥3 hypertension: n = 1); Hemorrhage, overall (n = 32; Grade≥3: n = 2); Hemorrhage, intracranial (n = 3; Grade≥3: n = 1); Wound-healing complications (n = 2; Grade≥3: n = 1); Venous thromboembolism (n = 8; Grade≥3: n = 7); Arterial thromboembolism (n = 5, Grade≥3: n = 2); Proteinuria (n = 2; Grade≥3: n = 1); Gastrointestinal perforation (n = 2; Grade≥3: n = 2); Reversible posterior leukoencephalopathy syndrome (n = 1, Grade≥3: n = 0); Aphasia (Grade≥3: n = 6); Confusional state (Grade≥3: n = 4); Convulsion (Grade≥3: n = 11); Diarrhea (Grade≥3: n = 4); Fatigue (Grade≥3: n = 7); Pneumonia (Grade≥3: n = 4); Pyramidal tract syndrome (Grade≥3: n = 4); Somnolence (Grade≥3: n = 4); Hypokalemia (Grade≥3: n = 6); Leukopenia (Grade≥3: n = 5); Lympyhopenia (Grade≥3: n = 6); Neutropenia (Grade≥3: n = 7)