scholarly journals Topical Corticosteroid Therapy for Facial Acneiform Eruption due to EGFR Inhibitors in Metastatic Colorectal Cancer Patients: A Randomized Controlled Trial Comparing Starting with a Very Strong or a Weak Topical Corticosteroid (FAEISS Study, NCCH1512, Colorectal Part)

2021 ◽  
Author(s):  
Katsuko Kikuchi ◽  
Naoya Yamazaki ◽  
Keiko Nozawa ◽  
Haruhiko Fukuda ◽  
Taro Shibata ◽  
...  
Keyword(s):  
Topical Corticosteroid ◽  
Controlled Trial ◽  
Growth Factor Receptor ◽  
Egfr Inhibitors ◽  
Term Care ◽  
Topical Corticosteroids ◽  
Acneiform Eruption ◽  
Epidermal Growth ◽  
Colorectal Cancer Patients ◽  
Clinical Trials Registry

Abstract Background: Althoughpre-emptive therapy with oral tetracycline, moisturizer, sunscreen and topical corticosteroid isuseful for preventing acneiform eruption (AfE) due to epidermal growth factor receptor (EGFR) inhibitors, no studies have examinedthe efficacy of topical corticosteroids themselves, or investigated the optimal strength of the corticosteroid for treating facial AfE (FAfE).Patients and Methods: Screened patients with RAS wild-typecolorectal cancerstarted pre-emptive therapy with oral minocycline and moisturizeron initiation of cetuximab or panitumumab therapy. Patients who developed grade 1 or 2 FAfEwere randomly allocated to two groups:a ranking-down (RD) group,started with a very strong corticosteroid, and serially ranked down every 2 weeks unless FAfE exacerbated, and a ranking-up (RU) group, started with a weak corticosteroid and serially ranked up at exacerbation. FAfE grade, patient quality of life, and adverse events (AEs) with topical corticosteroid were evaluated every 2 weeks.The primary endpoint was the total number of times grade 2 or higher FAfEidentified in thecentral review of the 8-weektreatment period.Results: No significant differences in total numbers of grade 2 or higher FAfE and inAEs caused by topical corticosteroids were observedbetweengroups during the 8-week. Incidence of grade 2 or higher FAfEwas tended to lower inthe RD group during the first 2 weeks.Conclusion: Considering long-term care of FAfE, the RU regimen appears suitableand should be considered the standard treatment for FAfEdue to EGFR inhibitor therapy. Trial registration: UMIN Clinical Trials Registry (UMIN000024113)

scholarly journals Severe and delayed-onset acneiform eruptions as an adverse reaction to regorafenib

2021 ◽  
Author(s):  
Haruhiko Otsuka ◽  
Takeshi Fukumoto ◽  
Naomi Kiyota ◽  
Chihiro Takemori ◽  
Haruki Jimbo ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Egfr Inhibitors ◽  
Multikinase Inhibitor ◽  
Delayed Onset ◽  
First Case ◽  
Acneiform Eruption ◽  
Epidermal Growth ◽  
Histopathologic Analysis ◽  
Third Line ◽  
Multiple Liver Metastases

Regorafenib is an oral multikinase inhibitor targeting several tyrosine kinase receptors including BRAF and epidermal growth factor receptor (EGFR), and is approved as a third-line treatment for metastatic gastrointestinal stromal tumor (GIST). While acneiform eruptions have been observed in patients receiving other BRAF and EGFR inhibitors, the commonly reported adverse reactions to regorafenib are fatigue and palmar-plantar erythrodysesthesia. Herein, we report, to the best of our knowledge, the first case who presented with a severe acneiform eruption 24 months after beginning regorafenib for the treatment of GIST. A 61-year-old woman developed GIST with multiple liver metastases, and she was treated with imatinib and sunitinib. However, these therapies were discontinued, and regorafenib was administered. Twenty-four months after beginning regorafenib, she developed an acneiform eruption on her back. Histopathologic analysis of a skin biopsy from the back revealed neutrophilic suppurative folliculitis. Therefore, she postponed regorafenib administration for 2 months and was treated with topical application of clindamycin phosphate hydrate, which was effective. Consistent with reported evidence that the presence of acneiform eruption and the efficacy of EGFR inhibitors are positively associated, regorafenib had good anticancer activity in our patient. Ultimately, we found that although regorafenib-associated skin toxicities usually appear within 1 month of treatment, patients potentially can present with delayed-onset acneiform eruptions even 24 months later.

scholarly journals Structure-based design of some quinazoline derivatives as epidermal growth factor receptor inhibitors

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Muhammad Tukur Ibrahim ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Sani Uba
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Growth Factor Receptor ◽  
Pharmacokinetic Profile ◽  
Egfr Inhibitors ◽  
Tyrosine Kinase Receptor ◽  
Egfr Tyrosine Kinase ◽  
Epidermal Growth

Abstract Background The discovery of epidermal growth factor receptor (EGFR) inhibitors for the treatment of lung cancer, most especially non-small cell lung cancer (NSCLC), was one of the major challenges encountered by the medicinal chemist in the world. The treatment of EGFR tyrosine kinase to manage NSCLCs becomes an urgent therapeutic necessity. NSCLC was the foremost cause of cancer mortality worldwide. Therefore, there is a need to develop more EGFR inhibitors due to the development of drug resistance by the mutation. This research is aimed at designing new EGFR inhibitors using a structure-based design approach. Structure-based drug design comprises several steps such as protein structure retrieval and preparation, ligand library preparation, docking, and structural modification on the best hit compound to design new ones. Result Molecular docking virtual screening on fifty sets of quinazoline derivatives/epidermal growth factor receptor inhibitors against their target protein (EGFR tyrosine kinase receptor PDB entry: 3IKA) and pharmacokinetic profile predictions were performed to identify hit compounds with promising affinities toward their target and good pharmacokinetic profiles. The hit compounds identified were compound 6 with a binding affinity of − 9.3 kcal/mol, compounds 5 and 8, each with a binding affinity of − 9.1 kcal/mol, respectively. The three hit compounds bound to EGFR tyrosine kinase receptor via four different types of interactions which include conventional hydrogen bond, carbon-hydrogen bond, electrostatic, and hydrophobic interactions, respectively. The best hit (compound 6) among the 3 hit compounds was retained as a template and used to design sixteen new EGFR inhibitors. The sixteen newly designed compounds were also docked into the active site of EGFR tyrosine kinase receptor to study their mode of interactions with the receptor. The binding affinities of these newly designed compounds range from − 9.5 kcal/mol to − 10.2 kcal/mol. The pharmacokinetic profile predictions of these newly designed compounds were further examined and found to be orally bioavailable with good absorption, low toxicity level, and permeable properties. Conclusion The sixteen newly designed EGFR inhibitors were found to have better binding affinities than the template used in the designing process and afatinib the positive control (an FDA approved EGFR inhibitor). None of these designed compounds was found to violate more than the permissible limit set by RO5. More so, the newly designed compounds were found to have good synthetic accessibility which indicates that these newly designed compounds can be easily synthesized in the laboratory.

Antibiotics in prevention of skin toxic reactions of epidermal growth factor receptor inhibitors (literature review)

2021 ◽  
pp. 8-11
Author(s):  
L. S. Kruglova ◽  
I. A. Koroleva
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Topical Therapy ◽  
Growth Factor Receptor ◽  
Skin Toxicity ◽  
Egfr Inhibitors ◽  
Tetracycline Antibiotics ◽  
Negative Effect ◽  
Epidermal Growth

The article is an overview and contains up-to-date information on the use of tetracycline antibiotics in the prevention of acne-like rash in patients receiving therapy with epidermal growth factor receptor inhibitors. According to studies, prevention of skin toxicity is necessary to maintain the effectiveness of the antitumor effect of EGFR inhibitors and to minimize the negative effect of adverse effects from the skin on the quality of life of patients. The use of tetracycline antibiotics in combination with topical therapy and photoprotection for the prevention of acne-like rash against the background of the use of EGFR inhibitors is a fairly safe method for long-term use. Of the antibacterial drugs for the prevention of acne-like rash, the most advisable is the appointment of doxycycline at a dose of 100 mg per day from the first day of taking EGFR inhibitors.

290 COMPARATIVE EFFICACY OF CORTICOSTEROIDS FORMULATIONS FOR THE MANAGEMENT OF EOSINOPHILIC OESOPHAGITIS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS.

2020 ◽  
Vol 33 (Supplement_1) ◽  
Author(s):  
C Ma ◽  
B Feagan ◽  
D Claveau ◽  
L Landry ◽  
V Baribeau ◽  
...  
Keyword(s):  
Topical Corticosteroid ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Adult Patients ◽  
Eosinophilic Oesophagitis ◽  
High Power Field ◽  
Topical Corticosteroids ◽  
Randomized Controlled ◽  
First Choice ◽  
Histological Remission

Abstract   Topical corticosteroids are the foundation of pharmacologic treatment for eosinophilic oesophagitis (EoE) and administered mainly as nebulized swallowed fluticasone or budesonide viscous solution (BVS). Recently, a budesonide orodispersible tablet (BOT) has been approved for the treatment of EoE. The ideal formulation of topical corticosteroid delivery is unclear. Therefore, we aimed to compare the efficacy of BOT with other topical corticosteroid formulations for achieving histological remission in adult patients with EoE in a network meta-analysis (NMA). Methods A systematic literature review was performed using Medline and EMBASE from 1990 to July 2019. Eligible studies evaluated adult patients with a diagnosis of EoE treated with a topical corticosteroid in a randomized controlled trial. The outcome of interest was the proportion of patients achieving induction of histological remission (peak esophageal eosinophil count <5 eosinophils/high-power field). Direct comparisons were performed using the Mantel–Haenszel method and an NMA was performed using a fixed effect Bayesian framework with Markov Chain Monte Carlo simulations. Heterogeneity between studies was analyzed using the Cochrane Q test and consistency was verified. Results The search yielded 321 references and 6 (447 patients) were included in the quantitative summary. In the NMA, all formulations of topical corticosteroids were associated with greater histological remission rates than placebo. BOT was associated with a significantly higher rate of histological remission compared to BVS (odds ratio [OR] = 4.9; 95% credible interval [CrI] = 1.4,19.1), fluticasone (OR = 7.4; 95%CrI = 1.7,34.5), nebulized swallowed budesonide (NSB) (OR = 25.0; 95%CrI = 2.9,247.2) and placebo (OR = 387.6; 95%CrI = 97.5,2275.6). Similar trends were shown in direct comparisons. Analysis of the ranking of treatment options based on probability of effectiveness found BOT to be most probable followed by BVS, fluticasone, NSB, and placebo, consecutively. Conclusion This NMA of randomized controlled trials suggests that BOT is significantly more likely to achieve histological remission in adult patients with EoE compared to BVS, fluticasone, and NSB. We hypothesize that the superiority of BOT is related to increased contact time and targeting all inflammatory sites in the oesophagus, in contrast to other formulations. This NMA suggest that BOT is the first choice therapy amongst topical corticosteroids for the management of EoE.

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