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Oesophageal cancer
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Nyree Griffin, Jason Dunn, Lee Alexander Grant
Two recent studies in which monoclonal antibodies (nimotuzumab and cetuximab) targeting epidermal growth factor receptor (EGFR) (nimotuzumab and cetuximab) were administered in combination with standard chemotherapy to patients with squamous cell carcinomas demonstrated potential benefits as a first- and second-line treatment strategy (85,86).
Molecular targeted agents for enhancing tumour response
Published in Michael C. Joiner, Albert J. van der Kogel, Basic Clinical Radiobiology, 2018
Michael Baumann, Mechthild Krause, Vincent Grégoire
Other monoclonal antibodies directed against the EGFR have been developed and are being tested in various clinical phases. Nimotuzumab (H-R3) is a humanized antibody that has been tested in a phase I trial in combination with radiotherapy in patients with locally advanced disease (20). A phase II trial is ongoing in HNSCC. In anaplastic astrocytoma and glioblastoma, combination of radiotherapy with Nimotuzumab led to longer patient survival compared to radiotherapy alone in a randomised phase II trial that unfortunately did not include standard radiochemotherapy as a control arm (61). The safety profile of Zalutumumab (HuMax-EGFr), a fully humanized monoclonal antibody, has been evaluated in patients with metastatic or recurrent HNSCC (4). This antibody is undergoing testing in concomitant association with radiotherapy for locally advanced HNSCC. Panitumumab (ABX-EGF) and matuzumab (EMD 72000) are also fully humanized antibodies against EGFR (28,38) and have been tested in various human tumours. Combination of Panitumumab with neoadjuvant radiochemotherapy in locally advanced rectal cancer leads to high gastrointestinal toxicity and pathological complete response rates of 21% and 18%, which appear higher as compared to similar trials on cetuximab; however, long-term survival has not been evaluated yet (34,56).
Anti-EGFR nimotuzumab for DIPG in recurrent or children with high grade glioma: 10 years
Published in Cut Adeya Adella, Stem Cell Oncology, 2018
U. Bone, R. Cabanas, G. Saurez-Martinez, T. Crombet Ramos, P. Lorenzo-Luaces, M. Massimino, U. Bartels, E. Bouffet, F. Bach, D. Reuter, R.A. Ilyas, R. Ellerson, N. Iznaga-Escobar
Nimotuzumab, formerly called h-R3, is a genetically engineered humanized mAb that recognizes an epitope located in the extracellular domain of human EGFR. It is an IgG1 isotype that was obtained by transplanting the complementary determining regions (CDR) of the murine anti-EGFR mAb ior egf/r3 (IgG2a) to a human framework assisted by computer modeling (Mateo, 1997).
Changes in T lymphocyte subsets in peripheral blood of patients with middle-advanced cervical cancer before and after nimotuzumab combined with concurrent chemoradiotherapy
Published in Journal of Obstetrics and Gynaecology, 2023
Man Ao, Pengyu Li, Dongxue Sun, Xiaojun Li, Shulei Xu, Yuntao Hao
CC represents highly-prevalent cancer in women, accounting for approximately 604,000 new cases, in addition to 342,000 deaths globally in 2020 (Sung et al. 2021). Current-day treatment modalities, such as CCRT have improved patients’ outcomes and reduced recurrence and death rates by about 30–50%, however, the vast majority of patients are in only partial remission or remission for merely a short period after treatment, with more than 35% of patients still presenting with tumours and experiencing recurrence and metastasis (W. Chen et al. 2019). Interestingly, an array of biologic agents targeting molecular pathways such as EGFR have garnered the attention of numerous researchers (Eskander & Tewari 2014). Indeed, nimotuzumab, an anti-EGFR monoclonal antibody, was recently indicated to exert anti-tumour activity primarily through anti-proliferation, anti-angiogenesis, and pro-apoptosis (Mazorra et al. 2018). Herein, the current study sought to explore the effect of nimotuzumab plus CCRT regime on patients with middle-advanced CC.
Advances in pharmacotherapy for head and neck cancer
Published in Expert Opinion on Pharmacotherapy, 2021
Shikhar kumar, Vanita Noronha, Vijay Patil, Amit Joshi, Nandini Menon, Kumar Prabhash
Nimotuzumab is a humanized immunoglobulin G1 isotype monoclonal antibody directed against the extracellular domain of EGFR [18]. Nimotuzumab has been studied in locally advanced HNSCC. A phase 3 single-center randomized trial evaluated the addition of nimotuzumab to radical chemoradiation [CRT, radiation 66–70 Grays, chemotherapy with weekly cisplatin 30 mg/m2]. Approximately 70% of patients in both arms had tumors that were negative for human papilloma virus (HPV). PFS was the primary endpoint. At a median follow up of 39.13 months, the addition of nimotuzumab resulted in a statistically superior 2-year PFS from 50.1% [95% CI,43.7–56.2] in the CRT arm to 61.8% [95% CI, 55.2–67.7] in the nimotuzumab + CRT arm [hazard ratio, 0.69; 95% CI, 0.53–0.89; P= .004]. The benefit of nimotuzumab was maintained in a post-hoc analysis even in patients who received a cumulative dose of cisplatin ≥200 mg/m2 [hazard ratio, 0.73; 95% CI, 0.54–0.98; P = 0.036]. However, this benefit came at the cost of a significant increase in grade 3/4 mucositis [66.7% vs 55.8%, p = 0.01] [19].
Induction of different cellular arrest and molecular responses in low EGFR expressing A549 and high EGFR expressing A431 tumor cells treated with various doses of 177Lu-Nimotuzumab
Published in International Journal of Radiation Biology, 2020
ShishuKant Suman, Rashmi Priya, Mythili Kameswaran
EGFR is overexpressed in majority of the solid malignancies and its activation enhances tumor growth, invasion, and metastasis (Normanno et al. 2006). Nimotuzumab is an EGFR-targeted monoclonal antibody that has demonstrated anti-tumor activity in preclinical and clinical trials with minimal side effects generally seen with other anti-EGFR antibodies like Cetuximab and Panitumumab (Rivera et al. 2008).177Lu-Nimotuzumab has been evaluated for its anti-tumor efficacy in different tumors expressing different levels of EGFR (Vera et al. 2011, 2012; Calzadaet al. 2012; Pandeyet al. 2019). It has also been reported that Nimotuzumab binds differently to different tumors depending on their level of EGFR expression. It binds with maximum affinity to A431c ells having high EGFR expression, as compared to H125, U1810, and A549 cancer cell lines that have intermediate levels of EGFR expression (Garrido et al. 2011). Nimotuzumab shows very little binding with MDA-MB-231 cells that have low expression of EGFR. Accordingly, the anti-tumor capacity of Nimotuzumab is higher or more potent in EGFR overexpressing tumors (Garrido et al. 2011; Tang et al. 2019).