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Cancer Immunology
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Osama Al Hamarneh, John Greenman
Seminal work by Bonner et al. reported that the administration of cetuximab with radiotherapy, when compared to radiotherapy alone, has significantly prolonged progression free survival without increasing the common toxic effects associated with radiotherapy to the head and neck in a multicentred phase III clinical trial.98 So far, cetuximab is the only approved antibody by FDA and NICE for use in patients with locally advanced HNSCC. In addition, a variety of other anti-EGFR agents such as the small molecule tyrosine kinase inhibitors (TKI) lapatinib, dacomitinib and afatinib and the anti-EGFR mAbzalutumumab, nimotuzumab and panitumumab, are currently under investigation in phase II and III clinical trials in different HNSCC therapeutic settings. The EGFR-targeting TKI erlotinib is currently in phase III development for oral cancer prevention (NLM Identifer NCT00402779), while bevacizumab, an anti VEGF monoclonal antibody, has been shown to produce favourable efficacy when combined with chemoradiotherapy for locally advanced HNSCC.101 Numerous other biological agents are in early stages of development for HNSCC treatment, including novel anti-EGFR mAb such as necitumumab, small-molecule TKIs (vandetanib, icotinib and dasatinib), and drugs (temsirolimus and everolimus). Overall, a wealth of clinical trial data are expected in the coming years, with the potential to modify significantly the approach to anti-EGFR therapy for HNSCC.102
Targeting the EGFR signaling pathway in cancer therapy: What’s new in 2023?
Published in Expert Opinion on Therapeutic Targets, 2023
Sushanta Halder, Soumi Basu, Shobhit P. Lall, Apar K. Ganti, Surinder K. Batra, Parthasarathy Seshacharyulu
Icotinib (BPI-2009 H/Conmana): Icotinib is an orally bioavailable quinazoline-based EGFR TKI that selectively blocks wild-type and several mutants of EGFR tyrosine kinase with a potent antineoplastic effect. In China, it was approved by SFDA in 2011, but the US FDA has yet to approve it due to a lack of clinical studies. In 2014, the US FDA issued a ‘May Proceed’ permission to conduct a phase I clinical trial with icotinib to treat EGFR-positive NSCLC patients. The dose of icotinib has been determined as 125 mg thrice a day for 6 weeks for locally advanced cervical cancer patients [67]. Icotinib was reported to be the highly antiproliferative, anti-apoptotic, and anti-EMT agent in NSCLC cells in both time- and concentration-dependent manner. It inhibits EMT by regulating EMT-related proteins, like E-cadherin, N-cadherin, Vimentin, and fibronectin [68]. Apart from its effect in NSCLC, it is found to be effective in cervical cancer, enhancing the radiotherapy effect in childhood nasopharyngeal carcinoma and improving radiosensitivity of biliary tract cancer and hepatocellular carcinoma [67,69–71]. A study of 1321 advanced-stage NSCLC patients confirmed the long-term treatment effect, safety, and tolerability of icotinib [72].
Monoclonal antibody as a targeting mediator for nanoparticle targeted delivery system for lung cancer
Published in Drug Delivery, 2022
Nasrul Wathoni, Lisa Efriani Puluhulawa, I Made Joni, Muchtaridi Muchtaridi, Ahmed Fouad Abdelwahab Mohammed, Khaled M. Elamin, Tiana Milanda, Dolih Gozali
Doxorubicin is encapsulated in polymeric nanoparticles comprised of amphipathic cationic starch and hyaluronic acid. The inclusion of erlotinib, apatinib, and icotinib, which are anti-EGFR ligands, were conducted to be evaluated on A549, NCI-H1975, and PC9 cells line. Rats were used as experimental animals for in vivo investigations. When compared to other ligands, the data showed that icotinib was the most effective. Icotinib nanoparticles had a particle size of 65.7 nm, which increased cytotoxic activity and prevented cancer cell types from migrating. The in vivo test findings revealed an increase in the concentration of nanoparticles at the target region and enhanced drug selectivity compared to the normal cells (Li et al., 2020). Anti-EGFR was also used to deliver paclitaxel palmitate nanoparticles. Cetuximab administration in this system increased A549-luc-C8 absorption, internalization, and therapeutic efficacy in vitro and in vivo in metastasis lung tumor (Karra et al., 2013).
Adjuvant therapy in non-small cell lung cancer: is targeted therapy joining the standard of care?
Published in Expert Review of Anticancer Therapy, 2021
Carolina Gabay, Alessandro Russo, Luis E. Raez, Christian Rolfo Cervetto
Recently, at the IASLC World Lung Cancer Congress (WCLC) 2020, the results of the EVIDENCE trial with another first-generation EGFR TKI approved in China, icotinib, were presented [27]. This was an open-label phase III trial, which included stages II–IIIA patients EGFRm+ to receive icotinib or 4 cycles of chemotherapy. The authors presented a planned interim analysis with a median follow-up of 24.9 months. The median DFS was superior in the experimental arm (47 months vs. 22.1 months). The use of icotinib was associated with a risk reduction for progression or death of 73%. For major protocol deviation, 39 of 322 recruited patients were excluded in trial analysis (more than 10% of the population). This represents an important limitation and a major concern on this trial. Furthermore, no information on post-treatment EGFR TKI exposure were available and again patients in the experimental arm did not receive platinum-based chemotherapy. As mentioned for EVAN and CTONG 1104 trials, the EVIDENCE trial has similar limitations for its interpretation. The primary endpoint was DFS, the experimental arm was not allowed to use chemotherapy, and it enrolled east-Asiatic patients.