Treatment of children with high grade glioma with nimotuzumab: A 5-y institutional experience

Cabanas, Ricardo; Saurez, Giselle; Rios, M De Los; Alert, J; Reyes, A. Raymundo; Valdés, José Miguel; González, María; Pedrayes, Jorge L; Ávila, M. Carmen Saborido; Herrera, Raiza; Infante, M. A.; Echevarria, Ernesto; Moreno, Myrna; Luaces, Patricia Lorenzo; Ramos, Tania Crombet

doi:10.4161/mabs.22970

Cited by 25 publications

(21 citation statements)

References 28 publications

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“…49 Nimotuzumab (humanized IgG1 monoclonal antibody against EGFR), used either alone or in combination with RT and chemotherapy in pHGG, was also well tolerated and showed a median survival time of 32.66 months and a 2-year survival rate of 54.2%. 50 In this study, nimotuzumab was given for a prolonged period of time in some cases (4 years), was tolerated, and showed no disease progression after discontinuation of treatment. 50 Antiangiogenic agents, such as thalidomide and its analog lenalidomide, have been tried in small groups of children with some promising results.…”

Section: Bevacizumab As a Frontline Therapeutic Agentmentioning

confidence: 76%

“…50 In this study, nimotuzumab was given for a prolonged period of time in some cases (4 years), was tolerated, and showed no disease progression after discontinuation of treatment. 50 Antiangiogenic agents, such as thalidomide and its analog lenalidomide, have been tried in small groups of children with some promising results. 51 There is an ongoing phase I trial testing lenalidomide in combination with RT for newly diagnosed pHGG (NCT-01222754).…”

Section: Bevacizumab As a Frontline Therapeutic Agentmentioning

confidence: 76%

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Management of high-grade gliomas in the pediatric patient: Past, present, and future

Vanan

Eisenstat

2014

Neuro-Oncology Practice

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High-grade gliomas (HGGs) constitute 15% of all primary brain tumors in children and adolescents. Routine histopathological diagnosis is based on tissue obtained from biopsy or, preferably, from the resected tumor itself. The majority of pediatric HGGs are clinically and biologically distinct from histologically similar adult malignant gliomas; these differences may explain the disparate responses to therapy and clinical outcomes when comparing children and adults with HGG. The recently proposed integrated genomic classification identifies 6 distinct biological subgroups of glioblastoma (GBM) throughout the age spectrum. Driver mutations in genes affecting histone H3.3 (K27M and G34R/V) coupled with mutations involving specific proteins (TP53, ATRX, DAXX, SETD2, ACVR1, FGFR1, NTRK) induce defects in chromatin remodeling and may play a central role in the genesis of many pediatric HGGs. Current clinical practice in pediatric HGGs includes surgical resection followed by radiation therapy (in children aged . 3 years) with concurrent and adjuvant chemotherapy with temozolomide. However, these multimodality treatment strategies have had a minimal impact on improving survival. Ongoing clinical trials are investigating new molecular targets, chemoradiation sensitization strategies, and immunotherapy. Future clinical trials of pediatric HGG will incorporate the distinction between GBM molecular subgroups and stratify patients using group-specific biomarkers.

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Section: Bevacizumab As a Frontline Therapeutic Agentmentioning

confidence: 76%

Section: Bevacizumab As a Frontline Therapeutic Agentmentioning

confidence: 76%

Management of high-grade gliomas in the pediatric patient: Past, present, and future

Vanan

Eisenstat

2014

Neuro-Oncology Practice

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“…14 antibody), either alone or with RT and CT, is the latest achievement. 6 It works against EGFR and has shown OS of 32.66 months and a 2-year survival rate of 54.2% in pediatric intracranial HGG. The pending administration of the histone deacetylase (HDAC) inhibitor 6 vorinostat in the treatment of recurrent GBM may be a new direction even in spinal GBM.…”

Section: Discussionmentioning

confidence: 97%

A systematic review of overall survival in pediatric primary glioblastoma multiforme of the spinal cord

Konar

Bir

Maiti

et al. 2017

PED

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OBJECTIVE The incidence of primary spinal cord glioblastoma multiforme (GBM) in the pediatric age group is very rare. Only a few case series and case reports have been published in the literature; therefore, overall survival (OS) outcome and the as-yet poorly defined management options are not discussed in detail. The authors performed a cumulative survival analysis of all reported cases of pediatric spinal cord GBM to identify the predictive factors related to final survival outcome. METHODS A comprehensive search for relevant articles was performed on PubMed's electronic database MEDLINE for the period from 1950 to 2015 using the search words “malignant spinal cord tumor” and “spinal glioblastoma multiforme.” This study was limited to patients younger than 18 years of age. Survival rates for children with various tumor locations and treatments were collected from the published articles and analyzed. RESULTS After an extensive literature search, 29 articles met the study inclusion criteria. From the detailed information in these articles, the authors found 53 children eligible for the survival analysis. The majority (45%) of the children were more than 12 years old. Thirty-four percent of the cases were between 7 and 12 years of age, and 21% were younger than 7 years. In the Kaplan-Meier survival analysis, children younger than 7 years of age had better survival (13 months) than the children older than 7 years (7–12 years: 10 months, > 12 years: 9 months; p = 0.01, log-rank test). Fifty-five percent of the children were female and 45% were male. A cervical tumor location (32%) was the most common, followed by thoracic (28.3%). Cervicothoracic (18.9%) and conus (18.8%) tumor locations shared the same percentage of cases. Cervical tumors had a worse outcome than tumors in other locations (p = 0.003, log-rank test). The most common presenting symptom was limb weakness (53%), followed by sensory disturbances (25%). Median OS was 10 months. The addition of adjuvant therapy (radiotherapy [RT] and/or chemotherapy [CT]) after surgery significantly improved OS (p = 0.01, log-rank test). Children who underwent gross-total resection and RT had better outcomes than those who underwent subtotal resection and RT (p = 0.04, log-rank test). Cerebrospinal fluid spread, hydrocephalus, brain metastasis, and spinal metastasis were not correlated with OS in primary spinal GBM. CONCLUSIONS Adjuvant therapy after surgery had a beneficial effect on overall outcome of spinal GBM in the pediatric age group. Gross-total resection followed by RT produced a better outcome than subtotal resection with RT. Further large-scale prospective study is required to establish the genetic and molecular factors related to OS in primary GBM of the spinal cord in pediatric patients.

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“…We tested the hypothesis that Nimotuzumab concomitant with RT will increase survival in DIPG. Nimotuzumab is a humanized monoclonal antibody, EGF/R3, 21,24,25,30 with a 10 fold affinity to EGFR. It has been reported that there are overexpression and of ERRB1/EGFR, 31,32 in DIPG suggesting that this tyrosine-kinasa receptor might be a target.…”

Section: Discussionmentioning

confidence: 99%

Long term survival in diffuse infiltrative brainstem gliomas in children and adolescents treated with radiotherapy and Nimotuzumab

Alert¹,

Chon²,

Valdés³

et al. 2018

IJRRT

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Background: Brainstem gliomas have a short survival time; chemotherapy has not improved outcome. We report the result obtained with the combination of Radiotherapy and the monoclonal antibody Nimotuzumab in a series of these tumors. Material and methods: 40 children and adolescents treated with irradiation and Nimotuzumab were included between Jan 2009 and December 2015, all with the diagnosis of diffuse infiltrative pontine gliomas (DIPG), irradiated at the Instituto Nacional de Oncologia y Radiobiologia, in Havana, Cuba. Nimotuzumab was applied during the period receiving Radiotherapy and them monthly for one year or more. Results: Median age at diagnosis was 7,9 years (range 3-18 years old); median survival was 18,4 months and Kaplan Meier survival was 42,5% at 2 years and 34,5% at 5 years, established till 9 years. Addition of Nimotuzumab was safe and well tolerated. Conclusion: Combination of Nimotuzumab and Radiotherapy is safe and could increase survival

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Treatment of children with high grade glioma with nimotuzumab: A 5-y institutional experience

Cited by 25 publications

References 28 publications

Management of high-grade gliomas in the pediatric patient: Past, present, and future

Management of high-grade gliomas in the pediatric patient: Past, present, and future

A systematic review of overall survival in pediatric primary glioblastoma multiforme of the spinal cord

Long term survival in diffuse infiltrative brainstem gliomas in children and adolescents treated with radiotherapy and Nimotuzumab

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