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Frontiers in Oncology 2020EGFR activation induces cell proliferation, neoformation of blood vessels, survival, and metastasis of the cancer cells. Nimotuzumab is an engineered, intermediate... (Review)
Review
EGFR activation induces cell proliferation, neoformation of blood vessels, survival, and metastasis of the cancer cells. Nimotuzumab is an engineered, intermediate affinity anti-EGFR antibody, that apart from other drugs in its class, is very safe and does not cause hypomagnesemia or grade 3-4 cutaneous rash. The antibody inhibits cell proliferation and angiogenesis, activates natural killer cells, stimulates dendritic cell maturation, and induces cytotoxic T cells. Nimotuzumab restores MHC-I expression on tumor cells, hindering one of the EGFR immune-escape ways. The antibody has been extensively studied in 7 clinical trials, concurrently with irradiation or irradiation plus chemotherapy in subjects with inoperable head and neck tumors. Nimotuzumab was safe and efficacious in unfit patients receiving irradiation alone and in subjects treated with cisplatin and radiotherapy. In patients with locally advanced squamous cell carcinomas of the head and neck, nimotuzumab in combination with low dose cisplatin and radiotherapy was superior to cisplatin and radiotherapy in progression free survival, disease free survival, and locoregional tumor control.
PubMed: 32537431
DOI: 10.3389/fonc.2020.00817 -
MAbs 2012Therapeutic monoclonal antibodies (mAbs) are currently being approved for marketing in Europe and the United States, as well as other countries, on a regular basis. As...
Therapeutic monoclonal antibodies (mAbs) are currently being approved for marketing in Europe and the United States, as well as other countries, on a regular basis. As more mAbs become available to physicians and patients, keeping track of the number, types, production cell lines, antigenic targets, and dates and locations of approvals has become challenging. Data are presented here for 34 mAbs that were approved in either Europe or the United States (US) as of March 2012, and nimotuzumab, which is marketed outside Europe and the US. Of the 34 mAbs, 28 (abciximab, rituximab, basiliximab, palivizumab, infliximab, trastuzumab, alemtuzumab, adalimumab, tositumomab-I131, cetuximab, ibrituximab tiuxetan, omalizumab, bevacizumab, natalizumab, ranibizumab, panitumumab, eculizumab, certolizumab pegol, golimumab, canakinumab, catumaxomab, ustekinumab, tocilizumab, ofatumumab, denosumab, belimumab, ipilimumab, brentuximab) are currently marketed in Europe or the US. Data for six therapeutic mAbs (muromonab-CD3, nebacumab, edrecolomab, daclizumab, gemtuzumab ozogamicin, efalizumab) that were approved but have been withdrawn or discontinued from marketing in Europe or the US are also included.
Topics: Animals; Antibodies, Monoclonal; Drug Approval; Europe; Humans; Immunotherapy; Marketing; Product Recalls and Withdrawals; United States
PubMed: 22531442
DOI: 10.4161/mabs.19931 -
Biomedicine & Pharmacotherapy =... Nov 2020Nasopharyngeal carcinoma (NPC) is a common malignant tumor in Southern China and South-East Asia. Regardless of initiative high response to radiotherapy, parts of... (Review)
Review
Nasopharyngeal carcinoma (NPC) is a common malignant tumor in Southern China and South-East Asia. Regardless of initiative high response to radiotherapy, parts of patients still have relapses and metastases. It is reported that epidermal growth factor receptor (EGFR) is highly expressed in most of NPC and is a poor prognostic factor. Targeting EGFR therapies including monoclonal antibodies and EGFR tyrosine kinase inhibitors (EGFR-TKIs), offer different benefits and toxicities for patients with NPC. Herein, we summarize the clinical evidence of anti-EGFR therapies in the management of NPC and provide a direction for the treatment and research of NPC in the future.
Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents; ErbB Receptors; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Prospective Studies; Protein Kinase Inhibitors; Retrospective Studies
PubMed: 32836074
DOI: 10.1016/j.biopha.2020.110649 -
Immunotherapy Nov 2021In COVID-19, EGFR production is upregulated in the alveolar epithelial cells. EGFR overexpression further activates STAT-3 and increases lung pathology. The EGFR...
In COVID-19, EGFR production is upregulated in the alveolar epithelial cells. EGFR overexpression further activates STAT-3 and increases lung pathology. The EGFR pathway is also one of the major nodes in pulmonary fibrosis. Nimotuzumab, a humanized anti-EGFR antibody, was used to treat three patients with severe or moderate COVID-19. The antibody was administered in combination with other drugs included in the national COVID-19 protocol. Nimotuzumab was well tolerated. IL-6 decreased from the first antibody infusion. Clinical symptoms significantly improved after nimotuzumab administration, and the CT scans at discharge showed major resolution of the lung lesions and no signs of fibrosis. Safe anti-EGFR antibodies like nimotuzumab may modulate COVID-19-associated hyperinflammation and prevent fibrosis. RPCEC00000369 (RPCEC rpcec.sld.cu).
PubMed: 34806405
DOI: 10.2217/imt-2021-0269 -
Cancer Metastasis Reviews Sep 2017Over 90% of head and neck cancers overexpress the epidermal growth factor receptor (EGFR). In diverse tumor types, EGFR overexpression has been associated with poorer... (Review)
Review
Over 90% of head and neck cancers overexpress the epidermal growth factor receptor (EGFR). In diverse tumor types, EGFR overexpression has been associated with poorer prognosis and outcomes. Therapies targeting EGFR include monoclonal antibodies, tyrosine kinase inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, and antisense gene therapy. Few EGFR-targeted therapeutics are approved for clinical use. The monoclonal antibody cetuximab is a Food and Drug Administration (FDA)-approved EGFR-targeted therapy, yet has exhibited modest benefit in clinical trials. The humanized monoclonal antibody nimotuzumab is also approved for head and neck cancers in Cuba, Argentina, Colombia, Peru, India, Ukraine, Ivory Coast, and Gabon in addition to nasopharyngeal cancers in China. Few other EGFR-targeted therapeutics for head and neck cancers have led to as significant responses as seen in lung carcinomas, for instance. Recent genome sequencing of head and neck tumors has helped identify patient subgroups with improved response to EGFR inhibitors, for example, cetuximab in patients with the KRAS-variant and the tyrosine kinase inhibitor erlotinib for tumors harboring MAPK1 mutations. Genome sequencing has furthermore broadened our understanding of dysregulated pathways, holding the potential to enhance the benefit derived from therapies targeting EGFR.
Topics: Animals; Carcinoma, Squamous Cell; ErbB Receptors; Genetic Therapy; Head and Neck Neoplasms; Humans; Molecular Targeted Therapy; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Squamous Cell Carcinoma of Head and Neck
PubMed: 28866730
DOI: 10.1007/s10555-017-9687-8 -
Cancer Control : Journal of the Moffitt... 2022Pediatric gliomas represent the most common brain tumor in children and its higher grades are associated with higher recurrence and low survival rate. All therapeutic...
INTRODUCTION
Pediatric gliomas represent the most common brain tumor in children and its higher grades are associated with higher recurrence and low survival rate. All therapeutic modalities are reported to be insufficient to achieve satisfactory result, with follow-up treatment such as adjuvant radiotherapy and chemotherapy recommended to increase survival and hinder tumor progression. Nimotuzumab is a monoclonal antibody that acts as an inhibitor of epidermal growth factor receptor found on the surface of glioma cells and had been studied for its usage in pediatric gliomas in recent years.
METHODS
A systematic review is performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A through literature search was conducted on PubMed, Scopus, Cochrane, and clinicaltrials.gov database. Articles were selected systematically based on the PRISMA protocol and reviewed completely. The relevant data were summarized and discussed. We measured overall survival, progression-free survival, and adverse Events (AE) for nimotuzumab usage as an adjunct therapy in pediatric glioma population.
RESULT
From 5 studies included for qualitative analysis, 151 patients are included with overall survival (OS) that vary from 3.2-22.8 mo, progression-free survival (PFS) from 1.7-21.6 mo, and relatively low serious adverse events (0-21) are recorded. Follow-up ranged from 2.4-66 mo with four studies reporting diffuse intrinsic pontine glioma (DIPG) patients and only one study reporting nimotuzumab usage in pediatric high-grade glioma (HGG) patients with better outcome in HGG patients than DIPG.
CONCLUSION
There are no significant differences in the PFS and OS of nimotuzumab as adjunct therapy for pediatric compared to result of standard therapy in majority of previous studies. There were also no differences in the AE of nimotuzumab for pediatric glioma between studies, and low event of serious adverse events indicating its safety. But still there is an evidence of possible benefit of nimotuzumab as adjuvant therapy in pediatric glioma. We recommend further studies with larger number of patients that may lead to possibly different results. There should also be more studies with better level of evidence to further validate the effect of nimozutumab on pediatric glioma.
Topics: Adolescent; Antibodies, Monoclonal, Humanized; Brain Neoplasms; Brain Stem Neoplasms; Child; Combined Modality Therapy; Glioma; Humans
PubMed: 35191733
DOI: 10.1177/10732748211053927 -
Annals of Translational Medicine Dec 2022Platinum-based concurrent chemoradiotherapy (CCRT) is the primary treatment for locally advanced cervical cancer (LACC). Improving the efficacy of LACC treatment is the...
BACKGROUND
Platinum-based concurrent chemoradiotherapy (CCRT) is the primary treatment for locally advanced cervical cancer (LACC). Improving the efficacy of LACC treatment is the focus of clinical research, and nimotuzumab combined with CCRT is a new research direction. This retrospective study aimed to investigate the efficacy and safety of nimotuzumab combined with CCRT compared with CCRT alone for treating LACC.
METHODS
Data from LACC patients treated at The Affiliated Hospital of Qingdao University from March 2017 to December 2019 were collected, and patients were assigned to either a nimotuzumab plus chemoradiotherapy (N + CCRT) group or a CCRT group. Baseline data were also collected. Patients were followed up every 3 to 6 months by imaging examination or telephone. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were complete response rate (CRR), objective response rate (ORR), and incidence of adverse events (AEs).
RESULTS
A total of 120 patients (65 in the N + CCRT group and 55 in the CCRT group) were enrolled, which baseline data were no statistical difference between the two groups (P>0.05). In the N + CCRT group, the 1-, 2-, and 3-year cumulative survival rates were 98.46%, 95.38%, and 90.50%, respectively, and the 1-, 2-, and 3-year cumulative PFS rates were 89.23%, 83.08%, and 79.73%, respectively. The CRR was 86.15% (56/65), and the ORR was 92.31% (60/65). In the CCRT group, the 1-, 2-, and 3-year cumulative survival rates were 94.55%, 87.27%, and 78.18%, respectively, and the 1-, 2-, and 3-year cumulative PFS rates were 81.82%, 69.09%, and 59.69%, respectively. The CRR was 70.91% (39/55), and the ORR was 87.27% (48/55). The CRR (86.15% 70.91%, P=0.040) and 3-year cumulative PFS rates (79.73% 59.69%, P=0.039) were significantly higher in the N + CCRT group than in the CCRT group. The incidences of various AEs were from 5.45% to 95.38%, without significant difference in AEs between the two groups (P>0.05).
CONCLUSIONS
Nimotuzumab combined with CCRT enhanced the PFS and CRR of LACC patients and was well tolerated. The results can provide reference for clinical treatment of LACC.
PubMed: 36660627
DOI: 10.21037/atm-22-5739 -
Frontiers in Public Health 2022EGFR signaling is an important regulator of SARS-CoV induced lung damage, inflammation and fibrosis. Nimotuzumab is a humanized anti-EGFR antibody registered for several...
EGFR signaling is an important regulator of SARS-CoV induced lung damage, inflammation and fibrosis. Nimotuzumab is a humanized anti-EGFR antibody registered for several cancer indications. An expanded access study was conducted to evaluate the safety and recovery rate of severe and critical patients with confirmed SARS-CoV-2 infection, treated with nimotuzumab in combination with the standard of care in the real-world scenario. The antibody was administered as an intravenous infusions every 72 h, up to 5 doses. In order to assess the impact of nimotuzumab, the recovery rate was compared with a paired retrospective cohort. Control patients received standard treatment according the national protocol but not nimotuzumab. Overall, 1,151 severe or critical patients received nimotuzumab in 21 hospitals of Cuba. Median age was 65 and 773 patients had at least one comorbidity. Nimotuzumab was very well-tolerated and mild or moderate adverse events were detected in 19 patients. 1,009 controls matching with the nimotuzumab patients, were selected using a "propensity score" method. The 14-day recovery rate of the nimotuzumab cohort was 72 vs. 42% in the control group. Controls had a higher mortality risk (RR 2.08, 95% CI: 1.79, 2.38) than the nimotuzumab treated patients. The attributable fraction was 0.52 (95% CI: 0.44%; 0.58), and indicates the proportion of deaths that were prevented with nimotuzumab. Our preliminary results suggest that nimotuzumab is a safe antibody that can reduce the mortality of severe and critical COVID-19 patients.
Topics: Cohort Studies; Humans; Retrospective Studies; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35937253
DOI: 10.3389/fpubh.2022.948520 -
Therapeutic Advances in Medical Oncology 2022Diffuse intrinsic pontine glioma (DIPG) is a fatal disease with a median overall survival (OS) of less than 12 months after diagnosis. Radiotherapy (RT) still remains...
BACKGROUND
Diffuse intrinsic pontine glioma (DIPG) is a fatal disease with a median overall survival (OS) of less than 12 months after diagnosis. Radiotherapy (RT) still remains the mainstay treatment. Several other therapeutic strategies have been attempted in the last years without a significant effect on OS. Although radiological imaging is the gold standard for DIPG diagnosis, the urgent need to improve the survival has led to the reconsideration of biopsy with the aim to better understand the molecular profile of DIPG and support personalized treatment.
METHODS
In this study, we present a single-center experience in treating DIPG patients at disease progression combining targeted therapies with standard of care. Biopsy was proposed to all patients at diagnosis or disease progression. First-line treatment included RT and nimotuzumab/vinorelbine or temozolomide. Immunohistochemistry-targeted research included study of mTOR/p-mTOR pathway and . Molecular analyses included polymerase chain reaction, followed by Sanger sequences and/or next-generation sequencing.
RESULTS
Based on the molecular profile, targeted therapy was administered in 9 out of 25 patients, while the remaining 16 patients were treated with standard of care. Personalized treatment included inhibition of the PI3K/AKT/mTOR pathway (5/9), PI3K/AKT/mTOR pathway and (1/9), (2/9) and (1/9); no severe side effects were reported during treatment. Response to treatment was evaluated according to Response Assessment in Pediatric Neuro-Oncology criteria, and the overall response rate within the cohort was 66%. Patients treated with targeted therapies were compared with the control cohort of 16 patients. Clinical and pathological characteristics of the two cohorts were homogeneous. Median OS in the personalized treatment and control cohort was 20.26 and 14.18 months, respectively ( = 0.032). In our experience, the treatment associated with the best OS was everolimus.
CONCLUSION
Despite the small simple size of our study, our data suggest a prognostic advantage and a safe profile of targeted therapies in DIPG patients, and we strongly advocate to reconsider the role of biopsy for these patients.
PubMed: 36090803
DOI: 10.1177/17588359221113693 -
OncoTargets and Therapy 2015High-grade gliomas (HGG) are extremely aggressive lesions and represent the most common primary malignant brain tumors without an effective therapy. Standard treatment... (Review)
Review
High-grade gliomas (HGG) are extremely aggressive lesions and represent the most common primary malignant brain tumors without an effective therapy. Standard treatment for HGG usually includes surgery followed by radiotherapy and chemotherapy. However, the prognosis of patients with HGG remains dismal. We review the humanized epidermal growth factor receptor (EGFR) and the major EGFR target drugs in HGG treatments, focusing on the EGFR antibody nimotuzumab as a new therapeutic strategy in HGG. We found that nimotuzumab with or without radiotherapy, chemotherapy in newly diagnosed or recurrent HGG, such as glioblastoma multiforme (GBM), anaplastic astrocytomas (AA), and diffuse intrinsic pontine glioma (DIPG), might improve the response rate or the survival time. In conclusion, nimotuzumab is a very well-tolerated drug with acceptable toxicity, and it may have promising value in the combination treatment. As a result, multiple center randomized controlled Phase III clinical trials need to be conducted to confirm the efficacy and toxicity for nimotuzumab in HGG.
PubMed: 25926743
DOI: 10.2147/OTT.S60032