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

BMC Cancer

Tania Crombet⁸  Ferdinand Bach⁶  Niurys de-Castro^1,11  Javier Ballesteros³  Patricia Lorenzo Luaces⁸  Juan Antonio Martell⁴  Martha González Griego⁴  Mauricio Catalá⁹  Jorge Juan Marinello⁷  José Alert⁷  Rafael Domíngez^1,13  Silvia Salva²  Nelson Quintanal⁵  Carolina Toledo^1,12  José Vaquer^1,14  Javier Figueredo⁹  Julio César Selva¹  Maria Teresa Solomón^1,10 

[1]Lucía Iñiguez Hospital, Holguin, Cuba

[2]Hermanos Ameijeiras Hospital, Havana, Cuba

[3]University of the Basque Country, Havana, Spain

[4]National Center for Clinical Trials, Havana, Cuba

[5]Luis Díaz Soto Hospital, Havana, Cuba

[6]Oncoscience AG, Wedel, Germany

[7]National Institute of Oncology and Radiobiology, Havana, Cuba

[8]Center of Molecular Immunology, PO BOX 16040, Havana 11600, Cuba

[9]Center for Medical and Surgical Research, Havana, Cuba

[10]Calixto García Hospital, Havana, Cuba

[11]Institute of Pharmacy and Food, Havana, Cuba

[12]Maria Curie Hospital, Havana, Cuba

[13]Saturnino Lora Hospital, Santiago de Cuba, Cuba

[14]Arnaldo Milián Hospital, Santa Clara, Cuba

关键词: Glioblastoma multiforme;    Anaplastic astrocytoma;    Adult glioma;    Monoclonal antibody;    EGFR;    Nimotuzumab;    High grade glioma (HGG);   

Others  :  1079691
DOI  :  10.1186/1471-2407-13-299

 received in 2012-07-13, accepted in 2013-06-14,  发布年份 2013

【 摘 要 】

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 webcite).

【 授权许可】

   
2013 Solomón et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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