BACKGROUND: The prognosis of patients bearing high grade glioma remains dismal. 
Epidermal Growth Factor Receptor (EGFR) is well validated as a primary 
contributor of glioma initiation and progression. Nimotuzumab is a humanized 
monoclonal antibody that recognizes the EGFR extracellular domain and reaches 
Central Nervous System tumors, in nonclinical and clinical setting. While it has 
similar activity when compared to other anti-EGFR antibodies, it does not induce 
skin toxicity or hypomagnesemia.
METHODS: A randomized, double blind, multicentric clinical trial was conducted 
in high grade glioma patients (41 anaplastic astrocytoma and 29 glioblastoma 
multiforme) that received radiotherapy plus nimotuzumab or placebo. Treatment 
and placebo groups were well-balanced for the most important prognostic 
variables. Patients received 6 weekly doses of 200 mg nimotuzumab or placebo 
together with irradiation as induction therapy. Maintenance treatment was given 
for 1 year with subsequent doses administered every 3 weeks. The objectives of 
this study were to assess the comparative overall survival, progression free 
survival, response rate, immunogenicity and safety.
RESULTS: The median cumulative dose was 3200 mg of nimotuzumab given over a 
median number of 16 doses. The combination of nimotuzumab and RT was 
well-tolerated. The most prevalent related adverse reactions included nausea, 
fever, tremors, anorexia and hepatic test alteration. No anti-idiotypic response 
was detected, confirming the antibody low immunogenicity. The mean and median 
survival time for subjects treated with nimotuzumab was 31.06 and 17.76 vs. 
21.07 and 12.63 months for the control group.
CONCLUSIONS: In this randomized trial, nimotuzumab showed an excellent safety 
profile and significant survival benefit in combination with irradiation.
TRIAL REGISTRATION: Cuban National Register for clinical trials (No. 1745) 
(http://registroclinico.sld.cu/ensayos).