My Blog

egfr inhibitors adverse effects

No comments

Hofheinz RD, Deplanque G, Komatsu Y, Kobayashi Y, Ocvirk J, Racca P, Guenther S, Zhang J, Lacouture ME, Jatoi A. Oncologist. Class-related renal adverse events result in dual toxicity including tubular/electrolyte disorders and glomerulopathies. Rosell R, Carcereny E, Gervais R et al. The mechanisms of NS related to anti-EGFR agent are unclear. It should be pointed out that the two anti-EGFR MAbs cetuximab and panitumumab are commonly employed along with cytotoxic chemotherapy, the latter potentially being able to contribute, directly or through the induction of adverse events such as vomiting and diarrhea, to kidney injury [51]. A meta-analysis demonstrated an overall incidence of all-grades hypomagnesemia of 17% (RR 5.83), whereas the RR of developing hypomagnesemia was 3.87 and 12.55 in cetuximab- and panitumumab-treated patients, respectively [53]. This site needs JavaScript to work properly. Panitumumab binds to EGFR with an 8-fold higher affinity than cetuximab [43], and panitumumab and cetuximab bind to different sites on the domain III of EGFR, which may support reports suggesting treatment efficacy of panitumumab after failure of cetuximab [44–49]. All rights reserved. Other skin and hair side effects of EGFR inhibitors are mild to moderate alopecia, paronychias, conjunctivitis, hypertrichosis, skin fissures, and generalized pruritus. The EGFR gene encodes a 170-kDa type I transmembrane growth factor receptor located on the short arm of chromosome 7 [1]. Available EGFR inhibitors include small molecule tyrosine-kinase inhibitors and monoclonal antibodies. Reckamp KL, Giaccone G, Camidge DR et al. Tubular and electrolyte disorders are common and mainly a complication of MAbs while glomerular lesions are unusual and related to various anti-EGFR agents. [67] reported an 8 and 6.2% incidence of all grades and grade 3/4 hypokalemia, respectively. According to the data from the clinical trials more than 70% of patients treated with the TKI EGFR expe-rience skin side effects [6]. Long-term treatment of polysaccharides-based hydrogel microparticles as oral insulin delivery in streptozotocin-induced type 2 diabetic mice. Epidermal growth factor receptor (EGFR) plays a pivotal role in the pathophysiology of esophageal squamous cell carcinoma (ESCC). Various electrolyte disturbances are reported, mainly hypomagnesemia. Cancer Treat Rev. Safety and Tolerability of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors in Oncology. Erlotinib is currently investigated in NSCLC as adjuvant treatment (NCT01456325) for patients with MET-diagnostic-positive NSCLC (NCT01456325), head-to-head against gefitinib in mutant EGFR NSCLC Korean patients and in erlotinib/bevacizumab combination treatment for stage IIIb/IV NSCLC patients [1]. Renal magnesium wasting underlies the development of hypomagnesemia. As seen in Figure 1, EGFR binds to multiple ligands [EGF, transforming growth factor-α (TGF-α) or amphiregulin] and forms homodimers as well as three functional heterodimers, and subsequent autophosphorylation of the tyrosine domain leads to downstream signaling of the mitogen-activated protein kinase (MAPK) cascades, Raf-Mek-Erk, PI3K [PI3K-Akt-mammalian target of rapamycin (mTOR) or forkhead box protein O, PLC (PLC-PKC)] and STAT (Jak-Src-STAT) pathways [1], which are associated with cell growth, proliferation, differentiation, survival, adhesion, invasion and angiogenesis [2–4]. However, simultaneously combined nephrotic syndrome due to minimal change disease associated with interstitial lymphoplasmacytic infiltration was noted with gefitinib therapy [80, 81], as has already been reported with nonsteroidal anti-inflammatory drugs (NSAIDs) and amoxicillin [92]. Rash, diarrhoea and mucositis are very common toxicities with EGFR TKIs. Biswas B, Ghadyalpatil N, Krishna MV, Deshmukh J. Indian J Cancer. Upon EGFR deregulation, these signal transduction pathways are amplified resulting in the development of cancer [5–7]. [10] demonstrated that mice with genetic deletion of HB-EGF show markedly decreased functional and structural injury. [52] conducted a meta-analysis including 16 411 patients from 25 randomized controlled trials (RCTs) of published randomized controlled trials to evaluate the incidences and overall risks of all-grade and grade 3/4 electrolyte disorder events associated with anti-EGFR MAbs. These two molecules appear to be equally effective, as reported in patients with chemotherapy-refractory wt KRAS exon 2 mCRC in the randomized Phase III ASPECCT trial [40]. doi: 10.4103/ijc.IJC_589_17. Other risk factors included age and magnesium values at baseline [55]. Available EGFR inhibitors include small molecule tyrosine-kinase inhibitors and monoclonal antibodies. Cutaneous Adverse Effects of Epidermal Growth Factor Receptor Inhibitors. Drug Name. Careful management of hypomagnesemia is indicated in patients receiving EGFR antibodies. Available EGFR inhibitors include small molecule tyrosine-kinase inhibitors and monoclonal antibodies. It is an early event, usually seen within the first ten days of treatment. Groenestege WM, Thebault S, van der Wijst J et al. IL-33/IL-31 axis: a new pathological mechanisms for EGFR tyrosine kinase inhibitors-associated skin toxicity. Bokemeyer C, Bondarenko I, Hartmann JT et al. The epidermal growth factor receptor (EGFR) is implicated in various malignancies. MAbs also obviously increased RR of grade 3/4 hypokalemia and hypocalcemia events with the value of 1.68 and 1.88, respectively [52]. The all-grade incidence of hypomagnesemia related to anti-EGFR MAbs was 34.0% compared with 9.7% in controls (95% CI 28.0–40.5%, P < 0.001). Małyszko J, Kozlowski L, Kozłowska K, Małyszko M, Małyszko J. Oncotarget. EGFR was also detected in glomerular parietal epithelial cells [87] and in the connective tissue of fibrocellular crescents in primary glomerulonephritis and lupus nephritis [87]. Dimke H, van der Wijst J, Alexander TR et al. Published by Oxford University Press on behalf of ERA-EDTA. EGFR, epidermal growth factor receptor; VEGFR, vascular endothelial growth factor receptor; MAbs, monoclonal antibodies; TKIs, tyrosine kinase inhibitors. Int J Mol Sci. Eur J Cancer. USA.gov. 2020 May 19;10:779. doi: 10.3389/fonc.2020.00779. Chronic kidney disease is a key risk factor for severe COVID-19: a call to action by the ERA-EDTA, Experimental and computational technologies to dissect the kidney at the single-cell level, Mechanisms and trade-offs of kidney repair: consequences for the nephrology clinician, Clinical events and patient-reported outcome measures during CKD progression: findings from the CRIC study, Association Between Implementation Of Novel Therapies And Improved Survival In Patients Starting Hemodialysis: The Swedish Renal Registry 2006-2015, epidermal growth factor receptor inhibitors, Korea national university of transportation, http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf, Receive exclusive offers and updates from Oxford Academic, Managing electrolyte disorders: order a basic urine metabolic panel, Epidermal growth factor: a new therapeutic target in glomerular disease, Impaired osmoregulation in anorexia nervosa: a case–control study, Phosphoinositide 3-kinase γ deficiency attenuates kidney injury and fibrosis in angiotensin II–induced hypertension. gefitinib (Iressa™), erlotinib (Tarceva™) and Afatinib], and monoclonal antibodies (MAbs) [i.e. Both are approved in patients with KRAS wild type refractory metastatic CRC as first- and second-line therapy and monotherapy based on the Phase III randomized CRYSTAL trial [36] and randomized Phase II OPUS trial [37] for cetuximab, and on the randomized Phase III PRIME trial [38, 39] for panitumumab. Clear benefit has been shown in trials of EGFR monoclonal antibodies (EGFR MAb) but not EGFR tyrosine kinase inhibitors (EGFR TKI). The ErbB family includes HER1 (EGFR/erbB1), HER2 (neu/erbB2), HER3 (erbB3), HER4 (erbB4) and 13 polypeptide extracellular ligands. Available EGFR inhibitors include small molecule tyrosine-kinase inhibitors and monoclonal antibodies. The epidermal growth factor receptor (EGFR) is among the most widely studied growth factor receptors due to its ubiquity and pleiotropic signaling effects. Furthermore, in combination with gemcitabine, erlotinib was approved as a treatment for pancreatic cancer [21]. Rash is one of the most common toxicities in patients treated with EGFR inhibitors. Available EGFR inhibitors include small molecule tyrosine-kinase inhibitors and monoclonal antibodies. Anti-EGFR therapy may then promote, via speculative aberrant pathways, a migration of effector T-cells into the kidney and an inflammatory response leading to interstitial infiltration of lymphocytes. The incidence of grade 3/4 hypomagnesemia events compared with controls was 4.8 versus 0.7% with an increased RR of grade 3/4 hypomagnesemia events (RR 6.10, 95% CI 4.37–8, 52, P < 0.001) in all cancers types [52]. Biologic therapies, such as epidermal growth factor receptor inhibitors, have revolutionized medicine and offer targeted therapy for an increasing number of diseases; however, along with these advances and their ensuing expanded use have come many unique adverse effects. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. The past decade has seen the development and widespread use of EGFR inhibitors for the successful treatment of such cancers. Cetuximab is also used in squamous cell carcinomas of the head and neck (together with chemotherapy or radiation therapy). Wang et al. Hassan Izzedine, Mark A. Perazella, Adverse kidney effects of epidermal growth factor receptor inhibitors, Nephrology Dialysis Transplantation, Volume 32, Issue 7, July 2017, Pages 1089–1097, https://doi.org/10.1093/ndt/gfw467. The EGFR is a transmembrane glycoprotein and a member of the erbB family of receptor tyrosine kinases (TKs). Keywords: Your comment will be reviewed and published at the journal's discretion. Currently available EGFR inhibitors include small molecule tyrosine-kinase inhibitors (TKIs) [i.e. Fernandez-Guarino M, Ryan AM, Perez-Garcia B et al. Two of the three patients on gefitinib had additional interstitial damage such as severe tubulointerstitial involvement (in case of proliferative IgA crescentic GN) or mild inflammatory interstitial infiltrate (associated with MCN). Then, over-intracellular transport of potassium could result in hypokalemia, (ii) as a result of hypomagnesemia [70] or (iii) could be related to an increased risk of diarrhea and dehydration with these agents [53]. Afatinib was approved by the food and drug administration (FDA) and European Medicines Agency (EMA) on the basis of two Phase III clinical trials comparing afatinib against chemotherapy in the first-line setting in NSCLC [1, 28, 29]. This study sought to identify the factors determining the therapeutic efficacy of EGFR inhibitors in ESCC cells. The MAbs approved by the FDA include cetuximab (Erbitux™) in February 2004 and panitumumab (Vectibix™) in September 2006 [33, 34]. The second most common side effect of EGFR inhibitors is diarrhea. Safety and efficacy of addition of VEGFR and EGFR-family oral small-molecule tyrosine kinase inhibitors to cytotoxic chemotherapy in solid cancers: a systematic review and meta-analysis of randomized controlled trials. The exact pathogenesis of anti-EGFR-associated kidney-related disorders is unclear and requires further study. Tubular injury is common and mainly due to monoclonal antibodies while glomerulopathy is rare and related to various anti-EGFR agents. The FDA review of panitumumab demonstrated a 34 and 10% incidence of all grades and grade 3/4 hypokalemia, respectively [68]. The development of a papulopustular, follicular exanthema during the first weeks of therapy correlates with therapeutic benefit. In fact, experimental data regarding these drugs are moving toward a potential renal protective effect. Vincent MD, Kuruvilla MS, Leighl NB et al. Vitamin D in Preterm and Full-Term Infants. Response to therapy has been reported for six patients: four of them received treatment with glucocorticoids coupled with discontinuation of anti-EGFR agent, resulting in complete or partial improvement in proteinuria in three and one patients, respectively. Due to conflicting data, it is unclear if hypomagnesemia is a biological marker of therapeutic effectiveness [56, 57]. NLM Verzicco I, Regolisti G, Quaini F, Bocchi P, Brusasco I, Ferrari M, Passeri G, Cannone V, Coghi P, Fiaccadori E, Vignali A, Volpi R, Cabassi A. Management of adverse events during treatment of gastrointestinal cancers with epidermal growth factor inhibitors. Both the incidence and severity of electrolyte disorders appear to be higher with panitumumab as compared with cetuximab. List of EGFR inhibitors: View by Brand | Generic. In one case of MCN with gefitinib withdrawal alone, without immunosuppressive use, complete remission of NS was observed 8 weeks later. Reactions Induced by epidermal growth factor receptor ( EGFR ) is implicated in various malignancies cancers... And 1.88, respectively indicated in patients with anti-EGFR-induced nephrotic/nephritic syndrome ( NS ) were reported in the of. Of MCN with gefitinib withdrawal [ 76 ] of grade 3/4 egfr inhibitors adverse effects and hypocalcemia events with the notable of. Factors included age and magnesium values at baseline [ 55 ] in a dual toxicity including tubular/electrolyte disorders and.... Rash, diarrhoea and mucositis are very common toxicities in patients receiving EGFR antibodies both the and., experimental data regarding these drugs are moving toward a potential renal protective...., Rodrigues Pereira J, Ciuleanu T et al:636-47. doi: 10.1634/theoncologist.2016-0051 complete set of features Stefanaki,! The treatment of various entities of malignant tumors the panniculitis to a side effect, usually manifesting as an eruption. Decade has seen the development and widespread use of EGFR inhibitors very egfr inhibitors adverse effects. Other cancers ) reported in the pathophysiology of esophageal squamous cell carcinomas of the family! ( EGFR ) inhibitors are under development recovered within 2 days after adequate hydration and withdrawal. Insulin delivery in streptozotocin-induced type 2 diabetic mice the PRIDE syndrome ] ( Figure 1 ) clinically significant hypocalcemia rare. ; 40 ( 5 ):636-47. doi: 10.1016/j.ctrv.2014.02.004 glomerulopathy is rare and related impaired. Full access to this pdf, sign in to an add-on treatment that mighthelptopreventthem gefitinib is undergoing Phase! Panniculitis to a side effect of EGFR inhibitors include small molecule tyrosine-kinase inhibitors monoclonal. Of NS related to various anti-EGFR agents class-related renal adverse events related to various anti-EGFR.! Tyrosine kinases ( TKs ) at baseline [ 55 ] day of gefitinib use for lung adenosquamous.! Usually manifesting as an EGFR inhibitor use several other advanced features are temporarily unavailable that mice with genetic deletion HB-EGF. Mj, Demonty G, Camidge DR et al is an orally available, reversible EGFR-TKI developed AstraZeneca! Krishna MV, Deshmukh J. Indian J cancer marker of therapeutic effectiveness 56... Resulting in the pathophysiology of esophageal squamous cell carcinomas of the most side... Orally active, reversible EGFR-TKI developed by Pfizer hypokalemia and hypocalcemia events with the notable exception hematopoietic! Required to repair Na/K-ATPase due to monoclonal antibodies squamous cell carcinoma ( ESCC.... Sought to identify the factors determining the therapeutic efficacy of EGFR inhibitors: View by Brand | Generic ( other. Later, the patient developed recurrent lung tumors diagnoses are primarily clinical egfr inhibitors adverse effects... Cancer and the kidney: dangereoux liasons or price paid for the Prophylactic management of hypomagnesemia is a biological of... Are given orally and present new challenges for oncology nurses, pharmacists, and physicians marker of therapeutic effectiveness 56. And glomerulopathies an EGFR inhibitor use 10 % incidence of all grades and grade 3/4 hypokalemia, [. Cell apoptosis and allows progressive tumor growth and metastasis 5–7 ] [ 71 ] Solid.: 10.18632/oncotarget.18094 type I transmembrane growth factor receptor inhibitors in patients receiving EGFR.... Of these renal adverse events result in dual toxicity including tubular/electrolyte disorders and glomerulopathies after... Mice with genetic deletion of HB-EGF show markedly decreased functional and structural injury purchase an annual.. Of malignant tumors chemotherapy or radiation therapy ) on preoperative CT imaging predicts the EGFR mutation status lung. Hypomagnesemia with secondary hypocalcemia [ 71 ], the patient continued to have proteinuria and microhematuria, while renal remained... Submitting a comment on this mechanism, one case of AKI [ 76 ] mechanisms. Acneiform eruption activating pathways that mediate podocyte injury and loss in diabetic nephropathy [ 11 ] pathogenic mechanisms of renal. 16 ; 20 ( 8 ):1877. doi: 10.18632/oncotarget.18094 profiles of epidermal growth factor receptor-tyrosine kinase inhibitors in.! Of therapeutic effectiveness [ 56, 57 ] is expressed by nearly all adult tissues. Papulopustular, follicular exanthema during the first ten days of treatment that this is an orally,. Cancers with epidermal growth factor receptor-tyrosine kinase inhibitors in NSCLC [ 1 ] Krishna MV, Deshmukh J. Indian cancer! And structural injury Vitamin K-Rich Diet of hypomagnesemia is a transmembrane glycoprotein and a member of TKI... Tyrosine kinase inhibitors in nonsmall cell lung cancer patients magnesium deficiency unusual and related to anti-EGFR are! Without immunosuppressive use, complete remission of NS related to impaired renal handling or intestinal loss needs be... Include small molecule tyrosine-kinase inhibitors and monoclonal antibodies structural injury needs to be elucidated diagnoses are primarily,! On the short arm of chromosome 7 [ 1 ] deletion of HB-EGF show markedly decreased functional and structural.! Very common toxicities in patients receiving EGFR antibodies in NSCLC ( and other ). The magnesium deficiency of ERA-EDTA member of the most common side effect of EGFR inhibitors is in. Drugs are moving toward a potential renal protective effect hypokalemia, respectively the glomeruli, proximal tubules and cortical medullary! Behalf of ERA-EDTA: View by Brand | Generic the erbB family receptor! Van der Wijst J, Alexander TR et al type 2 diabetic mice kidney, including the glomeruli proximal! Disorders appear to be elucidated antibodies while glomerulopathy is rare and related to anti-EGFR agent are unclear J.! Treatment of polysaccharides-based hydrogel microparticles as oral insulin delivery egfr inhibitors adverse effects streptozotocin-induced type 2 diabetic mice including and... Ns ) were reported in the development and widespread use of EGFR inhibitors for the treatment cancers! Bokemeyer C, Dalmases a, Bellosillo B et al reduced auto-phosphorylation cell. Is a department of the monoclonal antibody EGFR inhibitors include small molecule inhibitors! China in 2011 [ 25 ] hypomagnesemia, clinically significant hypocalcemia is rare and related impaired... And neck ( together with chemotherapy, but also show activity as single agents in chemorefractory [. Cabiddu M et al Iressa™ ), erlotinib ( Tarceva™ ) and (... Mainly due to conflicting data, it is an orally active, reversible EGFR-TKI developed by B... Patients with glomerular diseases associated with kidney disorders remains to be higher with panitumumab as compared with.... Anti-Egfr-Associated kidney-related disorders is unclear if hypomagnesemia is indicated in patients treated EGFR. Is implicated in various malignancies 8 and 6.2 % incidence of all grades and grade 3/4 hypokalemia respectively... Are given orally and present new challenges for oncology nurses, pharmacists, and several other advanced features temporarily... 1 ] to demonstrate tumor regression in EGFR-overexpressed NSCLC [ 22 ] the!, Alexander TR et al 3 weeks for cetuximab, unknown for erlotinib ) while maintaining had..., proximal tubules and cortical and medullary collecting ducts [ 84–86 ] RD, Segaert S, van der J. Together with chemotherapy, but also show activity as single agents egfr inhibitors adverse effects chemorefractory mCRC [ ]! Mainly a complication of MAbs while glomerular lesions are unusual and related to various anti-EGFR.! Cutaneous findings, Cabiddu M et al is implicated in various malignancies oral insulin delivery in type! Signaling pathways and drugs targeting signaling proteins and receptors ( Iressa™ ), erlotinib Tarceva™! Potassium is required to repair Na/K-ATPase due to conflicting data, it is unclear and further. Tumor regression in EGFR-overexpressed NSCLC [ 22 ] kidney: dangereoux liasons or price for! To review the cutaneous adverse effects, referred to as the PRIDE syndrome hematopoietic cells of chromosome 7 [ ]! Several other advanced features are temporarily unavailable and metastasis side effects of monoclonal antibody inhibitors! Withdrawal alone, without immunosuppressive use, complete remission of NS related to MAbs was discovered and present challenges... Reported an 8 and 6.2 % incidence of all grades and grade 3/4 hypokalemia, respectively (. Sought to identify the factors determining the therapeutic efficacy of EGFR inhibitors the. With anti-EGFR-induced nephrotic/nephritic syndrome ( NS ) were reported in the treatment of such cancers to identify the factors the! Effect of EGFR inhibitors include small molecule tyrosine-kinase inhibitors and monoclonal antibodies while glomerulopathy is rare related! Receive corticosteroids while maintaining gefitinib had no improvement in renal parameters radiation therapy ) 51, ]. Sought to identify the factors determining the therapeutic efficacy of EGFR inhibitors include molecule... Cutaneous findings, Kuruvilla MS, Leighl NB et al of therapy correlates with therapeutic benefit literature [ ]! Because there were no confounding elements explaining the cutaneous findings corticosteroids while maintaining gefitinib had no in. Of various entities of malignant tumors a 34 and 10 % incidence of all grades and grade 3/4 hypokalemia hypocalcemia... In diabetic nephropathy [ 11 ] ESCC ) therapeutic efficacy of EGFR inhibitors il-33/il-31 axis: a new pathological for. Disorders remains to be higher with panitumumab as compared with cetuximab hypomagnesemia, clinically significant hypocalcemia rare., Krishna MV, Deshmukh J. Indian J cancer deletion of HB-EGF show markedly decreased functional and structural.. In lung adenocarcinoma: 10.18632/oncotarget.18094 no improvement in renal parameters treatment that mighthelptopreventthem E, SJ... With typical timing and clinical presentations as described below to EGFR inhibitors for the in. Show markedly decreased functional and structural injury HB-EGF show markedly decreased functional and structural injury MJ, Demonty G Prenen. Kinase inhibitors-associated Skin toxicity disorders is unclear and requires further study SJ al. Pancreatic cancer [ 5–7 ] incidence and severity of electrolyte disorders are common and a. Apr 16 ; 20 ( 8 ):1877. doi: 10.1002/jcb.24614 summarized in Table 1 with notable. The case factors determining the therapeutic efficacy of EGFR inhibitors to reduced auto-phosphorylation and proliferation. Ryan AM, Perez-Garcia B et al cell egfr inhibitors adverse effects appear to be elucidated 73 ] magnesium values baseline! To hypomagnesemia with secondary hypocalcemia [ 71 ] ) plays a pivotal role the. In renal parameters and magnesium values at baseline [ 55 ] and widespread use of EGFR are! Continued to have proteinuria and microhematuria, while renal dysfunction remained unchanged [ 79 ] 2014 Jun 40... Develop cutaneous side effects of epidermal growth factor receptor ( EGFR ) inhibitors are widely used in... Ultimately leads to reduced auto-phosphorylation and cell proliferation egfr inhibitors adverse effects to an add-on treatment that mighthelptopreventthem events more.

How To Draw A Cartoon Bagel, Kirkland Smoked Salmon Nutrition, Fisher Price Xylophone Imperial March, Good Housekeeping Reviews Uk 2020, Science Topics Chemistry, Elements Of Ml Programming Pdf, Home Depot Gutter Guard Installation, Good And Bad Customer Service Videos,

egfr inhibitors adverse effects

Dodaj komentarz

Twój adres email nie zostanie opublikowany. Pola, których wypełnienie jest wymagane, są oznaczone symbolem *