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Table 1 Characteristics of the described cases of cetuximab-induced aseptic meningitis

From: Cetuximab-induced aseptic meningitis: case report and review of a rare adverse event

Case, Date Age range Indication for cetuximab Cetuximab dose (duration), premedication Symptoms (time onset), imaging Initial CSF analysis Follow-up CSF analysis Treatment, recovery Rechallenge
1, 2000 [8] N/R N/R 100 mg/m2 N/R N/A N/A N/R N/R
2, 2009 [10] 40–49 Recurrent laryngeal squamous cell carcinoma 400 mg/m2 (first administration 2 h), diphenhydramine 50 mg IV Frontal headache, 38.9 °C fever (few hours after infusion), N/R 2300/μl with 98 % neutrophils, protein 1.04 g/L, normal glucose level, negative cultures “Resolution of neutrophilic pleocytosis”, normal protein levels (day 4) Empirical antibiotic treatment, acyclovir, recovery N/R Negative rechallenge after 1 week (250 mg/m2, premedication: dexamethasone, diphenhydramine) without adverse events
3, 2009 [10] 40–49 Locally advanced squamous cell carcinoma of right tonsil 400 mg/m2 (first administration 2 h), diphenhydramine 50 mg IV Severe frontal headache, 39.4 °C fever, neck stiffness, photophobia (about 8 h after infusion), N/R 2267/μl with 90 % neutrophils, protein 1.46 g/L, normal glucose level, negative cultures “No white blood cells”, elevated but improved protein (0.69 g/L) Empirical antibiotic treatment, acyclovir, dexamethasone, recovery from meningeal symptoms after 12 days Negative rechallenge after 2 weeks (250 mg/m2, premedication: dexamethasone, diphenhydramine, famotidine) without adverse events
4, 2010 [13] 70–79 NSCLC (stage IIIA) 400 mg/m2 (first administration, duration N/R), N/R Severe headache, nausea, vomiting, neck stiffness (few hours after infusion), brain CT scan normal 528/μl with 87 % neutrophils, “modestly elevated protein”, normal glucose level N/A Empirical antibiotic treatment (stopped after infection was ruled out), recovery without neurological sequelae N/R
5, 2010 [13] 50–59 Metastatic NSCLC 400 mg/m2 (first administration, duration N/R), N/R Acute encephalopathy (few hours after infusion), brain CT scan and MRI normal cell count and fraction of neutrophils N/A, protein 1.16 g/L, glucose 2.8 mmol/L, negative cultures N/A Empirical antibiotic treatment (stopped after infection was ruled out), recovery within several days N/R
6, 2012 [9] 50–59 Squamous maxillary cancer (stage IVb) 400 mg/m2 (first administration), diphenhydramine 50 mg IV Frontal headache, neck discomfort, 39.9 °C fever (few hours after infusion), brain CT scan normal 1025/μl with 92 % neutrophils, protein 1.65 g/L, normal glucose level, negative bacterial culture, PCR (HSV) negative N/A Empirical antibiotic treatment, resolution of symptoms – no complications. Positive rechallenge after 4 weeks (250 mg/m2), recurrent CSF pleiocytosis (715/μl, 93 % neutrophils), protein 1.22 g/L, premedication: diphenhydramine. Rechallenge three and following without adverse events.
7, 2015 [11] 60–69 Recurrent advanced oropharyngeal squamous cell carcinoma 400 mg/m2 (first administration, 2 h), clemastine 2 mg oral Headache, mutism, hypertension, neck stiffness, 39.2 °C fever (about 9 h after infusion), brain CT scan and MRI non-diagnostic 1413/μl with 92 % neutrophils, protein 1.79 g/L, normal glucose level 3.5 mmol/L, negative cultures and serologies Cell count 1/μl, protein 0.68 g/L, normal glucose level 4.0 mmol/L Empirical antibiotic treatment, dexamethasone (stopped after infection was ruled out), myoclonic jerks and NCSE after 3 days, recovery within 14 days The patient refused rechallenge.
8, 2015 [12] 50–59 Tonsillar squamous cell cancer 400 mg/m2 (first administration) Frontal headache (10/10 in severity), fever (1 h after infusion), brain CT scan 473/μl with 80 % neutrophils in tube 1 and 500/μl with 62 % neutrophilsin tube 4. 150 and 50 cells/μL red blood cells, protein 1,28 g/L, normal glucose level N/A Empirical antibiotic treatment for 4 days (stopped after infection was ruled out). Symptomatic improvement after 2 days and recovery within 4 days Negative rechallenge after 7 days, the patient received a second dose of cetuximab at 250 mg/m2 without adverse events.
9, 2015 Present case 60–69 Locally advanced laryngeal squamous cell carcinoma 400 mg/m2 (first administration, 2 h), dexchlorpheniramine 5 mg IV Headache, photophobia, neck stiffness, vomiting, nausea (few hours after infusion), N/A Leukocytes count 4100/μL with 90 % of neutrophils, 6/μL red blood cells, protein 1.5 g/L, normal glucose level in 3.16 mmol/L., negative viral and bacterial cultures. N/A Empirical antibiotic treatment for 7 days, recovery without sequelae within several days Negative rechallenge after 28 days (250 mg/m2, premedication: methylprednisolone, dexchlorpheniramine) without adverse events.