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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Radiotherapy plus nimotuzumab or placebo in the treatment of high grade glioma patients: results from a randomized, double blind trial

Authors: Maria Teresa Solomón, Julio César Selva, Javier Figueredo, José Vaquer, Carolina Toledo, Nelson Quintanal, Silvia Salva, Rafael Domíngez, José Alert, Jorge Juan Marinello, Mauricio Catalá, Martha González Griego, Juan Antonio Martell, Patricia Lorenzo Luaces, Javier Ballesteros, Niurys de-Castro, Ferdinand Bach, Tania Crombet

Published in: BMC Cancer | Issue 1/2013

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Abstract

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).
Appendix
Available only for authorised users
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Metadata
Title
Radiotherapy plus nimotuzumab or placebo in the treatment of high grade glioma patients: results from a randomized, double blind trial
Authors
Maria Teresa Solomón
Julio César Selva
Javier Figueredo
José Vaquer
Carolina Toledo
Nelson Quintanal
Silvia Salva
Rafael Domíngez
José Alert
Jorge Juan Marinello
Mauricio Catalá
Martha González Griego
Juan Antonio Martell
Patricia Lorenzo Luaces
Javier Ballesteros
Niurys de-Castro
Ferdinand Bach
Tania Crombet
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-299

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