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Squamous cell carcinoma of the head and neck is the sixth most common cancer worldwide. However, malignant tumors of the middle ear are extremely rare. Squamous cell carcinoma is the most common histologic type of tumor in this area, accounting for more than 50% of cases. Complex anatomical and topographic features of the inner ear and inapparent clinical symptoms result in delayed diagnosis of this disease. A case of a patient with highly differentiated middle ear squamous cell carcinoma is presented. The patient received complex treatment, including drug antitumor therapy according to the TPEx protocol: docetaxel + cisplatin + cetuximab. Being highly effective, this protocol requires a multidisciplinary approach in order to ensure maximum safety of therapy. The case illustrates the classic “portrait” of a patient with recurrent or metastatic squamous cell carcinoma of the head and neck and also provides a comprehensive description of the spectrum of adverse events faced by such patients and their oncologists. Based on this clinical case, the features of management of such adverse events are analyzed.

Background/Objectives: Epidermal growth factor receptor (EGFR) plays a vital role in cell proliferation and survival, with its overexpression linked to various malignancies, including non-small cell lung cancer (NSCLC). Although EGFR tyrosine kinase inhibitors (TKIs) are a key therapeutic strategy, acquired resistance and relapse remain challenges. This study aimed to synthesize and evaluate novel rhenium-based complexes incorporating EGFR TKIs to enhance anticancer efficacy, particularly in radiosensitization. Methods: We synthesized a rhenium tricarbonyl complex (Complex 2) and its 99mTc analog (Complex 2') by incorporating triphenylphosphine instead of bromine as the monodentate ligand and P F 6 − as the counter-ion, resulting in a positively charged compound that forms cationic structures. Cytotoxicity and EGFR inhibition were evaluated in A431 cells overexpressing EGFR using MTT assays, Western blotting, and flow cytometry. Radiosensitization was tested through MTT and clonogenic assays. The 99mTc complex's radiochemical yield, stability, and lipophilicity were also assessed. Results: Complex 2 exhibited significant cytotoxicity with an IC50 of 2.6 μM and EGFR phosphorylation inhibition with an IC50 of 130.6 nM. Both complex 1 and 2 induced G0/G1 cell cycle arrest, with Complex 2 causing apoptosis. Radiosensitization was observed at doses above 2 Gy. Complex 2' demonstrated high stability and favorable lipophilicity (LogD7.4 3.2), showing 12% cellular uptake after 30 min. Conclusions: Complexes 2 and 2' show promise as dual-function anticancer agents, offering EGFR inhibition, apoptosis induction, and radiosensitization. Their potential as radiopharmaceuticals warrants further in-depth investigation in preclinical models. [ABSTRACT FROM AUTHOR]

The advent of targeted drug therapy has greatly changed the treatment landscape of advanced non-small cell lung cancer(NSCLC), but the cardioxic side effects of targeted drug anti-cancer therapy seriously affect the prognosis of NSCLC, and it has become the second leading cause of death in cancer patients. Therefore, early identification of the cardiotoxic side effects of targeted drugs is crucial for the prevention and treatment of cardiovascular diseases. The cardiotoxic side effects that may be caused by novel targeted drugs epidermal growth factor receptor inhibitors, including thromboembolic events, heart failure, cardiomyopathy, arrhythmia and hypertension, are discussed, and the mechanisms of their respective adverse cardiovascular reactions are summarized, to provide useful recommendations for cardiacmanagement of patients with advanced lung cancer to maximize treatment outcomes for lung cancer survivors. Clinicians need to balance the risk-benefit ratio between targeted therapy for malignant tumors and drug-induced cardiotoxicity, and evaluate and monitor TKIs-induced cardiotoxicity through electrocardiogram, cardiac imaging, biomarkers, etc., so as to remove the susceptibility risk factors as soon as possible and provide a reference for the clinical use of such drugs in the treatment of malignant tumors. [ABSTRACT FROM AUTHOR]

Napapat Pongbangpho, Kumutnart Chanprapaph, Wimolsiri Iamsumang Division of Dermatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Wimolsiri Iamsumang, Division of Dermatology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Rajthevi, Bangkok, 10400, Thailand, Tel +662-201-1141, Fax +662-201-1211, Email i.wimolsiri@hotmail.comAbstract: Panitumumab is a recombinant, fully humanized immunoglobulin G2 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). It is approved for the first- and second-line treatment of advanced wild-type KRAS colorectal cancer. Although common cutaneous side effects include acneiform dermatitis, folliculitis, and xerosis, ocular toxicities have occasionally been reported. Herein, we report the case of an 81-year-old Thai female with chemorefractory advanced stage sigmoid colon cancer who developed isolated periorbital dermatitis following treatment with panitumumab plus modified FOLFOX6. The cutaneous adverse reaction recurred after subsequent infusions; however, it was alleviated by topical therapy. To our knowledge, panitumumab-induced periorbital dermatitis is exceptionally rare. To raise awareness of potential periocular cutaneous side effects in patients taking EGFR inhibitors, the published literature regarding periorbital dermatitis induced by these agents has also been reviewed in this article. Periorbital dermatitis should be considered as a potential cutaneous reaction following panitumumab administration, and should be promptly treated.Keywords: colorectal cancer, cutaneous adverse drug reaction, epidermal growth factor receptor inhibitors, panitumumab, periorbital rash

The epidermal growth factor receptor (EGFR) tyrosine kinase plays an important role in tumor formation and growth by mediating cell growth and other physiological processes. Therefore, EGFR is a promising target for the treatment of cancer. In this work, we combined ligand‐based and structure‐based virtual screening methods to identify novel EGFR inhibitors from a library of more than 103 thousand compounds. We first obtained hundreds of compounds with similar physiochemical properties through 3D molecular shape and electrostatic similarity screening with potent inhibitors AEE788 and Afatinib as queries. Next, we identified compounds with strong binding affinities to the EGFR pocket through molecular docking, which makes good use of the structure information of the receptor. After molecular scaffold analysis, our bioassay confirmed 13 compounds with EGFR inhibitory activity and three compounds had IC50 values below 1000 nM. In addition, we collected 5371 EGFR inhibitors from online databases, and clustered them into 7 groups by K‐means method using their ECFP4 fingerprints as input. Each cluster had typical molecular fragments and corresponding activity characteristics, which could guide the design of EGFR inhibitors, and we concluded that the fragments from some of the hits are indicated in the highly active scaffolds. [ABSTRACT FROM AUTHOR]

Background/Objectives: Epidermal growth factor receptor (EGFR) plays a vital role in cell proliferation and survival, with its overexpression linked to various malignancies, including non-small cell lung cancer (NSCLC). Although EGFR tyrosine kinase inhibitors (TKIs) are a key therapeutic strategy, acquired resistance and relapse remain challenges. This study aimed to synthesize and evaluate novel rhenium-based complexes incorporating EGFR TKIs to enhance anticancer efficacy, particularly in radiosensitization. Methods: We synthesized a rhenium tricarbonyl complex (Complex 2) and its 99mTc analog (Complex 2’) by incorporating triphenylphosphine instead of bromine as the monodentate ligand and PF6− as the counter-ion, resulting in a positively charged compound that forms cationic structures. Cytotoxicity and EGFR inhibition were evaluated in A431 cells overexpressing EGFR using MTT assays, Western blotting, and flow cytometry. Radiosensitization was tested through MTT and clonogenic assays. The 99mTc complex’s radiochemical yield, stability, and lipophilicity were also assessed. Results: Complex 2 exhibited significant cytotoxicity with an IC50 of 2.6 μM and EGFR phosphorylation inhibition with an IC50 of 130.6 nM. Both complex 1 and 2 induced G0/G1 cell cycle arrest, with Complex 2 causing apoptosis. Radiosensitization was observed at doses above 2 Gy. Complex 2’ demonstrated high stability and favorable lipophilicity (LogD7.4 3.2), showing 12% cellular uptake after 30 min. Conclusions: Complexes 2 and 2’ show promise as dual-function anticancer agents, offering EGFR inhibition, apoptosis induction, and radiosensitization. Their potential as radiopharmaceuticals warrants further in-depth investigation in preclinical models.

Abstract Background While cancer is a risk factor for developing thromboembolism, so is the use of molecularly targeted therapies. This study aimed to determine whether thromboembolism incidence differed between vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitor use in patients with unresectable advanced or recurrent colorectal cancer, and to compare the risk of thromboembolism caused by cancer and the use of molecular targeted therapy drugs. Main body We retrospectively evaluated patients with unresectable advanced or recurrent colorectal cancer who were treated with a cytotoxic anticancer drug and a VEGF or EGFR inhibitor combination between April 2016 and October 2021. Patients were compared in terms of the regimen administered, thromboembolism occurrence during the first-line treatment period, patient background, and clinical laboratory values. Of the 179 included patients, 12 of 134 (8.9%) in the VEGF-inhibitor group and 8 of 45 (17.8%) in the EGFR-inhibitor group developed thromboembolism, with no significant difference between the groups (P = 0.11). There was no significant difference in time to thromboembolism between patients in the VEGF- inhibitor group and patients in the EGFR-inhibitor group (P = 0.206). The cutoff value determined by a receiver operating characteristic analysis for the occurrence of thromboembolism was one point. Multivariate analysis using the occurrence of thromboembolism as the response variable identified at least one risk factor for thromboembolism (odds ratio = 4.17, P = 0.006, 95% confidence interval = 1.51–11.50). Molecular targeted therapies were not identified as a risk factor. Conclusions Although the small sample size, there was no difference in the incidence of thromboembolism between the two molecular-targeted therapies in first-line treatment of patients with unresectable advanced or recurrent colorectal cancer. Our results suggest that risk factors for thromboembolism may be more strongly influenced by cancer itself than by the use of molecularly targeted therapies.

Epidermal growth factor receptor inhibitors (EGFRIs) induced cutaneous toxicity is a common adverse event (AE), although it is not as severe as major cancers, we still need to pay enough attention to them. Therefore, it is necessary to evaluate the diversity of EGFRI class drugs. The objective of this study was to conduct a scientific and systematic investigation into the correlation between EGFRI and cutaneous toxicities. The data accessed from the FDA adverse event reporting system database (FAERS) encompass a time frame spanning from January 2013 to March 2023. By utilizing reporting odds ratios (RORs), information components (ICs), proportional reporting ratios (PRRs), and chi-squared (χ2), the relationship between drugs and adverse reactions was evaluated through disproportionality analysis. Within the FAERS database, a total of 29,559 skin adverse events were recorded. A robust indication of the correlation between EGFRI and elderly patients (≥65 years) was identified. Among EGFRIs, erlotinib accounted for the largest proportion of skin adverse events (39.72%). Rash, dry skin, and pruritus ranked top among all preferred terms, and signals such as rash, skin lesions, and acneiform dermatitis were detected in every single drug. Clinicians should guide patients customize the treatment plan for each patient.

Background: While cancer is a risk factor for developing thromboembolism, so is the use of molecularly targeted therapies. This study aimed to determine whether thromboembolism incidence differed between vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitor use in patients with unresectable advanced or recurrent colorectal cancer, and to compare the risk of thromboembolism caused by cancer and the use of molecular targeted therapy drugs. Main body: We retrospectively evaluated patients with unresectable advanced or recurrent colorectal cancer who were treated with a cytotoxic anticancer drug and a VEGF or EGFR inhibitor combination between April 2016 and October 2021. Patients were compared in terms of the regimen administered, thromboembolism occurrence during the first-line treatment period, patient background, and clinical laboratory values. Of the 179 included patients, 12 of 134 (8.9%) in the VEGF-inhibitor group and 8 of 45 (17.8%) in the EGFR-inhibitor group developed thromboembolism, with no significant difference between the groups (P = 0.11). There was no significant difference in time to thromboembolism between patients in the VEGF- inhibitor group and patients in the EGFR-inhibitor group (P = 0.206). The cutoff value determined by a receiver operating characteristic analysis for the occurrence of thromboembolism was one point. Multivariate analysis using the occurrence of thromboembolism as the response variable identified at least one risk factor for thromboembolism (odds ratio = 4.17, P = 0.006, 95% confidence interval = 1.51–11.50). Molecular targeted therapies were not identified as a risk factor. Conclusions: Although the small sample size, there was no difference in the incidence of thromboembolism between the two molecular-targeted therapies in first-line treatment of patients with unresectable advanced or recurrent colorectal cancer. Our results suggest that risk factors for thromboembolism may be more strongly influenced by cancer itself than by the use of molecularly targeted therapies. [ABSTRACT FROM AUTHOR]

Abstract Background The combination of antiangiogenic agents with epidermal growth factor receptor inhibitors (EGFR‐TKIs) and chemotherapy with EGFR‐TKIs are the most common combination treatment options in epidermal growth factor receptor (EGFR) positive non‐small cell lung cancer (NSCLC). This network meta‐analysis was performed to evaluate the differences between them. Methods We searched the PubMed, EMBASE and the Cochrane Controlled Trials Register up to August 2022. The primary outcomes were progression‐free survival (PFS) and objective response rate (ORR). The secondary endpoints were overall survival (OS), disease control rate (DCR) and adverse events (AEs). The data of hazard ratio (HR) or risk ratio (RR) with their corresponding 95% confidence intervals (CIs) were extracted in the studies. A network meta‐analysis (NMA) was used to indirectly compare the efficacy and safety of antiangiogenic agents plus EGFR‐TKIs and chemotherapy plus EGFR‐TKIs. Results Pooled data of included studies were demonstrated that chemotherapy plus EGFR‐TKIs had a benefit in ORR compared to antiangiogenic agents plus EGFR‐TKIs in patients with EGFR mutated NSCLC (RR = 1.1, 95% CI: 1.0–1.2). However, there were no significant differences in PFS, OS and DCR between in the two group (PFS: HR = 1.0, 95% CI: 0.74–1.6; OS: HR = 0.78, 95% CI: 0.45–1.5; DCR: RR = 1.0, 95% CI: 0.94–1.1). The common treatment‐related AEs in the two groups were relatively manageable. Conclusion Based on the efficacy and safety, the combination of chemotherapy with EGFR‐TKIs is considered the best combination treatment options in advanced NSCLC with EGFR mutation.

Background: The combination of antiangiogenic agents with epidermal growth factor receptor inhibitors (EGFR‐TKIs) and chemotherapy with EGFR‐TKIs are the most common combination treatment options in epidermal growth factor receptor (EGFR) positive non‐small cell lung cancer (NSCLC). This network meta‐analysis was performed to evaluate the differences between them. Methods: We searched the PubMed, EMBASE and the Cochrane Controlled Trials Register up to August 2022. The primary outcomes were progression‐free survival (PFS) and objective response rate (ORR). The secondary endpoints were overall survival (OS), disease control rate (DCR) and adverse events (AEs). The data of hazard ratio (HR) or risk ratio (RR) with their corresponding 95% confidence intervals (CIs) were extracted in the studies. A network meta‐analysis (NMA) was used to indirectly compare the efficacy and safety of antiangiogenic agents plus EGFR‐TKIs and chemotherapy plus EGFR‐TKIs. Results: Pooled data of included studies were demonstrated that chemotherapy plus EGFR‐TKIs had a benefit in ORR compared to antiangiogenic agents plus EGFR‐TKIs in patients with EGFR mutated NSCLC (RR = 1.1, 95% CI: 1.0–1.2). However, there were no significant differences in PFS, OS and DCR between in the two group (PFS: HR = 1.0, 95% CI: 0.74–1.6; OS: HR = 0.78, 95% CI: 0.45–1.5; DCR: RR = 1.0, 95% CI: 0.94–1.1). The common treatment‐related AEs in the two groups were relatively manageable. Conclusion: Based on the efficacy and safety, the combination of chemotherapy with EGFR‐TKIs is considered the best combination treatment options in advanced NSCLC with EGFR mutation. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor inhibitors (EGFR) have a high rate of class-specific dermatologic adverse events. Supportive treatment of dermatologic adverse events decreases their severity, minimizes the need for dose de-escalation / discontinuation of targeted therapy, improves commitment to anticancer treatment and patient’s quality of life. Close interdisciplinary cooperation between oncologists and dermatologists is a key to the successful management of patients treated with EGFR. This article highlights current approaches to classification, concepts of pathogenesis and clinical course of EGFR-associated dermatologic adverse events, current and promising prophylactic and therapeutic strategies to manage these adverse events.

Epidermal growth factor receptor inhibitors (EGFRi) are approved for treating various cancers. Given that EGFR signaling is crucial for normal skin growth and repair, inhibiting this pathway can disrupt skin homeostasis and integrity. Although generally well tolerated, molecularly targeted therapies can lead to skin-related adverse effects that significantly impact patients' quality of life, often resulting in treatment interruptions. The most common cutaneous reaction associated with EGFRi is a diffuse, papulopustular acneiform eruption. Management strategies can be tailored based on the severity of the condition and may include topical corticosteroids, topical and oral antibiotics, and systemic corticosteroid therapy. Moreover, consistent evidence supports the effectiveness of systemic retinoids at lower doses than those typically prescribed for acne vulgaris, advocating for their use when other treatments have failed. Herein, we present the case of a 71-year-old male with advanced colorectal cancer who was treated with panitumumab and subsequently developed a generalized papulopustular eruption three weeks after initiating therapy. The patient reported pruritus, a burning sensation, and hyperesthesia, which significantly impacted his daily activities. Physical examination revealed folliculocentric erythematous pustules and papules covering more than 30% of his body surface area (including the face, scalp, thorax, and extremities), along with xerosis, painful nasal and oral mucosal erosions, paronychia, and trichomegaly. Initial treatment with topical and systemic antibiotics, topical and systemic corticosteroids, and general skin care yielded poor results, with recurring moderate to severe eruptions occurring every 7 to 10 days. After three months and with approval from the oncology team, isotretinoin therapy (10 mg/day) was initiated under close monitoring of laboratory parameters. This approach achieved effective therapeutic control within one month, allowing the continuation of oncologic treatment without necessitating any dose modifications. In such cases, dermatologists play a vital role in managing these adverse reactions, ensuring that effective treatments enable patients to continue lifesaving oncologic therapies., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bălăceanu-Gurău et al.)

Epidermal growth factor receptor inhibitors(EGFRIs) improve the survival rate of patients with EGFR-mutated non-small cell lung cancer significantly, but may simutaneously cause a series of adverse dermatological events. In traditional Chinese medicine(TCM) theory, EGFRIs could be classified as of dryness-heat nature that injures yin, therefore the adverse dermatological events are caused by heat-toxin of EGFRIs. Heat underpins the whole process of EGFR-mutated non-small cell lung cancer, and the disease location is the lung. The whole course of the disease can be divided into three stages, including wind-heat pattern combined with dampness-heat at the initial stage, yin deficiency and blood dryness pattern at the middle stage, and pattern of dual yin-yang deficiency at the advanced stage. Therefore, in the treatment of EGFRIs-related adverse dermatological events, on the basis of clearing heat, the therapeutic method differ in different stages, i. e. dispelling wind and eliminating dampness, nourishing yin and blood, as well as nourishing the spleen and kidney at the initial, middle, and advanced stages respectively. The formulae include Zhiyang Pingfu(Itch-relieving and Skin-soothing) Formula, Zizao Yangrong Tang(Dryness-relieving and Skin-Nourishing Decoction), Jingui Shenqi Wan(Golden Cabinet’s Kidney Qi Pill) and so on. [ABSTRACT FROM AUTHOR]

Introduction: The PRIDE (Papulopustules and/or paronychia, Regulatory abnormalities of hair growth, Itching, Dryness due to EGFR inhibition) syndrome is a cutaneous adverse effect of EGFR inhibitors. Case report: We describe an 80-year-old man, who presented with itchy papules over the suprapubic region and hair growth over the lower back for 1 month. He was diagnosed with squamous cell carcinoma of the lung, and was treated with oral gefitinib 250 mg daily for 4 months. Cutaneous examination revealed generalized xerosis, discrete papules and pustules with overlying yellow crusts over the suprapubic region, and paronychia with dystrophic changes over the right first and third toe nail. Localised hypertrichosis was seen over the back in midline lumbosacral region. Conclusions: Hair overgrowth such as trichomegaly and hypertrichosis have been described in the PRIDE syndrome. We describe an atypical presentation of the syndrome with lumbosacral hypertrichosis. [ABSTRACT FROM AUTHOR]

Pharmacists are an integral part of medication management, with the positive impact of their clinical services in patient outcomes previously studied and reported in literature. The roles and responsibilities of pharmacists continue to expand, including optimizing patient medication and health outcomes related to complex oral anticancer drugs.To evaluate the impact of a pharmacist-managed oral chemotherapy clinic in patients with non-small cell lung cancer (NSCLC) taking oral epidermal growth factor receptor inhibitor (EGFRi) regimens within an integrated healthcare delivery system.This was an observational cohort study using data from Kaiser Permanente Northern and Southern California regions on adult patients who received oncology pharmacist-managed care compared to patients with usual care. Patients were newly initiated with EGFRi therapy to treat NSCLC between 2017 and 2019. The follow-up period was defined as the time from index date (first sold date of EGFRi) to December 2020 or end of membership or death, whichever occurred first. Primary outcome measures included adherence to EGFRi, frequency of imaging during drug exposure, and presence of imaging prior to treatment change. Outcomes were analyzed with Chi-square test for categorical variables, and Student's t-test or Wilcoxon rank-sum test for continuous variables.There were 613 patients in the pharmacist-managed group and 714 patients in the usual care group. Overall, the mean age was 68.2 ± 11.3 years, and 65.1% were female. In the pharmacist-managed group, there was a significantly higher mean proportion of days covered (PDC) during the first three months of therapy (0.86 ± 0.24 vs 0.82 ± 0.36, p = 0.01) and a higher percentage of patients who were adherent to EGFRi therapy (with PDC ≥0.80) during the drug exposure period (95.8% vs 92.4%, p = 0.01). The rate of computed tomography (CT) and magnetic resonance imaging (MRI) during drug exposure was higher in the pharmacist-managed group compared to the usual care group (31.8% vs 20.7%, p < 0.01) with a higher number of mean scans completed per patient (1.15 ± 2.42 vs 0.62 ± 1.63, p < 0.01) and per patient-year (2.60 ± 7.27 vs 1.58 ± 5.95, p < 0.01). Overall, 66.2% of patients had a treatment change, with a higher percentage of patients in the pharmacist-managed group who completed a CT or MRI scan prior to treatment change (36.3% vs 26.3%, p < 0.01). Additionally, the median time between the scan and treatment change was shorter for patients with pharmacist-managed care (1.8 vs 4 months, p = 0.04).Clinical pharmacy services contributed to improved adherence, higher rates of imaging, and shorter time between imaging and treatment changes in NSCLC patients who were taking EGFRi regimens. [ABSTRACT FROM AUTHOR]

We evaluated the efficacy and safety of red light LED as an adjuvant treatment for epidermal growth factor receptor inhibitor-induced paronychia. Eight patients were recruited in this randomized, single-blinded controlled trial. They were randomized to receive red-light on one hand or foot 2–3 times/week for 6 weeks while the contralateral side served as controls. The standard treatments were continued. Erythema and lesion elevation observed by Anthera® 3D, severity and pain scores were obtained at weeks 0, 2, 4, 6, and 8. The red light group showed significantly lower erythema, severity, and pain scores at weeks 4, 6, and 8. The elevation was significantly lower in the red light group at every follow-up visit. No adverse events occurred. Red light therapy may be an option as adjunctive treatment for EGFRi-induced paronychia. [ABSTRACT FROM AUTHOR]

Background: Skin rash is the most common adverse effect associated with epidermal growth factor receptor inhibitors (EGFRIs). The study has observed the efficacy and safety of Zhiyang Pingfu Liquid in the treatment of EGFRIs-related moderate and severe rash. Methods: Patients suffering from EGFRIs-related moderate to severe rash were enrolled and then randomly divided into the treatment group and the control group, receiving Zhiyang Pingfu Liquid and placebo liquid respectively combined with minocycline and methylprednisolone recommended by guideline for 14 days. Changes in rash grades were observed, as well as the dosage of minocycline. Blood routine examination and liver and kidney function were evaluated to observe the safety of Zhiyang Pingfu Liquid. The total response of rash included complete response (CR) and partial response (PR). And the effective rate of rash was the percentage of CR and PR in the total cases. Results: A total of 54 out of 58 patients finished the study with 27 patients in each group. The effective rates of rash among the treatment group and the control group were 81.48% and 55.56% after 14 days treatment (P =.040). The treatment group had a lower dosage of minocycline compared with the control group. The median total dose of oral minocycline administration was 1000 mg in the treatment group and 1400 mg in the control group. Conclusion: Zhiyang Pingfu Liquid can effectively improve the moderate and severe EGFRIs-induced rash, and reduce the use of minocycline, as well as the side reactions brought by minocycline. However, larger randomized controlled trials are needed to verify these findings. Clinical Trial Registration: The trial was registered on the Chinese Clinical Trial Registry, the registration number is ChiCTR1800017053. [ABSTRACT FROM AUTHOR]

Purpose: To determine the risk and incidence of keratitis following treatment with epidermal growth factor receptor inhibitors (EGFRi) and subtypes of EGFRi-associated keratitis., Methods: This multi-center cohort study included EGFRi-treated patients and non-users with lung cancer between 2010 and 2023. EGFRi included first-generation agent gefitinib and erlotinib, second-generation agent afatinib, and third-generation agent osimertinib. The primary outcome was new-onset keratitis. Cox proportional hazard models with multivariable adjustment were applied to determine the effect of EGFRi on keratitis over time. Subgroup analyses were conducted, stratified by agents of EGFRi. Sub-outcome analyses were performed to identify the subtypes of EGFRi-associated keratitis., Results: A total of 1549 EGFRi-treated patients and 6146 non-users were included. 38 (2.5%) EGFRi-treated patients developed keratitis. The incidence of keratitis in EGFRi-treated patients was significantly higher than that in controls (incidence rate, IR, per 1000 person-years = 14.7 vs 4.49, p < 0.0001). EGFRi-treated patients presented with an increased risk for keratitis (adjusted hazard ratio, aHR = 3.14, 95% CI = 1.85-5.35, p < 0.001). Erlotinib (aHR = 2.64, 95% CI = 1.35-5.15, p = 0.004), afatinib (aHR = 4.42, 95% CI = 2.17-9.02, p < 0.001), and osimertinib (aHR = 4.67, 95% CI = 1.60-13.64, p = 0.005), but not gefitinib (aHR = 2.30, 95% CI = 0.96-5.55, p = 0.063), significantly contributed to the risk of keratitis. Subtypes of EGFRi-associated keratitis included corneal ulcer (IR = 2.31 vs 0.166, p < 0.0001) and keratoconjunctivitis (IR = 9.27 vs 2.91, p < 0.0001). None of the EGFRi-treated patients developed perforated corneal ulcer, interstitial and deep keratitis, or corneal neovascularization., Conclusion: Treatment with EGFRi was associated with an increased risk of keratitis. Ocular toxicity of EGFRi was highest for third-generation agents, followed by second-generation agents, and then first-generation agents., Competing Interests: Declaration of competing interest All authors declared no competing interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Epidermal growth factor receptor (EGFR) inhibitors are routinely used in advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, their use is associated with gastrointestinal and cutaneous toxicities, including acneiform eruptions, pruritus, xerosis, nail and hair changes. Aside from reducing patients' quality of life, such cutaneous reactions have a considerable impact on the oncologic treatment given that dose reduction or even drug discontinuation may be necessary, especially for the severe forms. Objectives: To assess the incidence, impact on treatment and management of EGFR inhibitor-related cutaneous reactions in patients with NSCLC. Methods: We conducted a prospective observational study on 87 consecutive patients with advanced NSCLC treated with EGFR-tyrosine kinase inhibitors from January to December 2019. Patients who developed mucocutaneous reactions were evaluated and treated by both oncologists and dermatologists, and underwent dermatologic follow-up until resolution of the cutaneous reaction. Demographic and clinical data were collected for each patient, and the severity of the cutaneous reaction was graded using the Common Terminology Criteria for Adverse Events. Results: Seventy-one patients (81.6%) developed cutaneous reactions. The number of cutaneous reactions per patient was 1 in 37%, 2 in 41% and 3 or more in 22%. The most common cutaneous reactions included acneiform eruptions (56.3%), xerosis ± asteatotic eczema (48.3%), nail changes (39.1%), mucositis (29.9%), pruritus (24.1%) and hair changes (12.6%). Afatinib was associated with a higher rate of nail changes and mucositis (p < 0.01 and p < 0.005, respectively) compared to other agents, while no patient-related predictive factors were identified. Dose reduction was performed in 18% of patients. Multidisciplinary management involving dermatologists allowed to resume the drug in all patients who had discontinued it due to the cutaneous reactions. Conclusions: A multidisciplinary approach to EGFR inhibitor-related cutaneous reactions is advantageous and can reduce the need to discontinue oncologic treatment. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to evaluate the efficacy of Traditional Chinese Medicine (TCM) in the treatment of rash caused by epidermal growth factor receptor inhibitors (EGFRIs). Materials and Methods: Foreign language database (such as PubMed, Web of Science, Cochrane Library, EMBASE) and Chinese language database (such as China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals [VIP], Wangfang, CBM disc) were searched for all trials of TCM in the treatment of rash caused by EGFRIs until January of 2019. We also looked through the references of relevant studies to supplement additional trials. The SPSS 25.0 was used for statistics of TCM with high frequency, and Review Manager 5.3 was used for meta-analysis. Results: A total of 22 studies were included in the study. We selected TCM whose frequency were >3.0%. They were Lonicera japonica(金银花), Licorice Roots Northwest Origin(生甘草), Cortex Dictamni(白鲜皮), Radix Sophorae Flavescentis(苦参), Schizonepeta(荆芥), Saposhnikovia Divaricate(防风). The meta-analysis revealed that the efficacy of TCM in treating EGFRIs-related rash was better than that of Western medicine or none. Conclusions: TCM could significantly relieve rash caused by EGFRIs, which is worth popularizing. Moreover, the mechanism deserves to be further explored.

Introduction: Evolution of targeted molecular therapies has greatly improved patient survival in cancer. Gefitinib is an oral, reversible, epidermal growth factor receptor inhibitor used in advance non-small cell lung cancer. Skin rashes and diarrhea are common adverse effects associated with gefitinib. However, electrolytes disorders are rarely reported with gefitinib, particularly hyponatremia. Case report: We describe a 65-year-old male with metastatic non-small cell lung cancer treated with gefitinib for the last three weeks. He presented to our hospital with complaints of acute onset drowsiness. On evaluation of drowsiness, patient was diagnosed with severe hyponatremia. Management and outcome: After ruling out other common causes of hyponatremia, gefitinib was attributed as a cause of hyponatremia. Gefitinib was immediately stopped and IV hypertonic saline (3% sodium chloride) was started due to severe symptomatic hyponatremia. After seven days of cessation of gefitinib, he became asymptomatic with normalisation of serum sodium levels. Discussion: Hyponatremia in cancer patients is associated with poor prognosis and prolonged hospital stay. Possibility of gefitinib-induced hyponatremia should be considered in order to achieve early diagnosis and prevent significant mortality in cancer patients. [ABSTRACT FROM AUTHOR]

The advent of targeted drug therapy has greatly changed the treatment landscape of advanced non-small cell lung cancer(NSCLC), but the cardioxic side effects of targeted drug anti-cancer therapy seriously affect the prognosis of NSCLC, and it has become the second leading cause of death in cancer patients. Therefore, early identification of the cardiotoxic side effects of targeted drugs is crucial for the prevention and treatment of cardiovascular diseases. The cardiotoxic side effects that may be caused by novel targeted drugs epidermal growth factor receptor inhibitors, including thromboembolic events, heart failure, cardiomyopathy, arrhythmia and hypertension, are discussed, and the mechanisms of their respective adverse cardiovascular reactions are summarized, to provide useful recommendations for cardiac management of patients with advanced lung cancer to maximize treatment outcomes for lung cancer survivors. Clinicians need to balance the risk-benefit ratio between targeted therapy for malignant tumors and drug-induced cardiotoxicity, and evaluate and monitor TKIs-induced cardiotoxicity through electrocardiogram, cardiac imaging, biomarkers, etc., so as to remove the susceptibility risk factors as soon as possible and provide a reference for the clinical use of such drugs in the treatment of malignant tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Qiu, Deng and Wan.)

Background: Tyrosine kinase inhibitors (TKIs) are standard treatment options for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Increasing clinical investigations have explored the value of EGFR-TKIs plus antiangiogenic drugs as the first-line treatment for EGFR-mutated NSCLC.Methods: We systematically searched PubMed, Cochrane Library, and EMBASE for randomized controlled trials (RCTs) investigating EGFR-TKIs administered with or without antiangiogenic agents for advanced EGFR-mutated NSCLC. The latest RCT that was presented orally at the 2019 European Society for Medical Oncology Congress was obtained online. The endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rates (DCRs), and grade 3 or higher adverse events (AEs).Results: We included seven articles on five trials with 1,226 patients. The interventions for the experimental group were the first-generation EGFR-TKI erlotinib combined with bevacizumab (four studies) or ramucirumab (one study), and erlotinib monotherapy (four studies) or erlotinib plus placebo (one study) for the control group. All studies reached their primary study endpoints (i.e., PFS). Compared to erlotinib monotherapy, erlotinib plus antiangiogenic agents remarkably prolonged PFS [hazard ratio (HR) = 0.59, 95% confidence interval (CI) = 0.51–0.69, P = 0.000]; however, ORR, DCR, and OS were similar between the two groups. The overall grade 3–5 AEs increased in combination group (OR = 5.772, 95% CI = 2.38–13.94, P = 0.000), particularly the incidence of diarrhea (OR = 2.51, 95% CI = 1.21–5.23, P = 0.014), acneiform (OR = 1.815, 95% CI = 1.084–3.037, P = 0.023), hypertension (OR = 6.77, 95% CI = 3.62–12.66, P = 0.000), and proteinuria (OR = 13.48, 95% CI = 4.11–44.22, P = 0.000). Additionally, subgroup analysis demonstrated that Asian patients could significantly benefit from combination therapy (HR = 0.59, 95% CI = 0.50–0.69, P = 0.000). Patients with exon 19 deletions (HR = 0.61, 95% CI = 0.49–0.75, P = 0.000) and 21 Leu858Arg mutations (HR = 0.59, 95% CI = 0.47–0.73, P = 0.000) had almost equivalent PFS benefits when treated with double-blocking therapy. Patients with brain metastases at baseline in the combination group had a trend toward better PFS (HR = 0.55, 95% CI = 0.30–1.01, P = 0.001).Conclusions: Erlotinib plus bevacizumab or ramucirumab in EFGR-mutated NSCLC first-line setting yielded remarkable PFS benefits; however, this was accompanied by higher AEs. Epidermal growth factor receptor–TKI plus antiangiogenic agent therapy may be considered a new option for advanced EGFR-mutated NSCLC patients.

BackgroundPatients with locally advanced rectal cancer (LARC) are at higher risk of local and distant recurrence and are thus more vulnerable to metastatic diseases. Neoadjuvant chemoradiotherapy (nCRT) and subsequent curative resection with total mesorectal excision (TME) followed by adjuvant chemotherapy have been recommended by the National Comprehensive Cancer Network (NCCN) guidelines as standard of care for LARC patients. However, the efficacy of the addition of epidermal growth factor receptor (EGFR) inhibitors in kirsten rat sarcoma viral oncogene (KRAS)-wild type LARC patients remains uncertain.MaterialsPubMed, Embase, and Web of Science were searched to retrieve records on the application of EGFR inhibitors in a neoadjuvant setting for LARC patients. pCR was used as surrogate endpoint to perform data synthesis in a single-arm setting.ResultsTen cohorts covering 540 subjects were eligible in this systematic review. The pooled pCR rate for EGFR inhibitors was 15% (95% confidence interval (95% CI), 11–20%; I2 = 55.2%); the pooled estimates of Grade 3/4 diarrhea, Grade 3/4 hand–foot syndrome, Grade 3/4 acneiform rash were 17% (95% CI, 4–34%; I2 = 93.3%), 2% (95% CI, 0–5%; I2 = 13.7%), and 15% (95% CI, 9–22%; I2 = 65.4%), respectively.ConclusionThe addition of EGFR inhibitors in the nCRT for KRAS-wild type LARC patients provides comparable efficacy and acceptable safety. However, the results should be interpreted cautiously due to the small amount of relevant data and need further confirmation by more future studies.

Epidermal growth factor receptor inhibitors (EGFRs) are chemotherapeutic agents used in multiple solid organ malignity. These medications have common dermatological side effects, particularly papulopustular (PPL) lesions. The management of the diagnosis and treatment processes for such side effects may facilitate the continuation of chemotherapy and enhance the patient's quality of life. The objective of this study is to report the cutaneous side effects of EGFR inhibitors and to share treatment methods for such side effects. In this prospective study, 59 patients using EGFR due to breast and colorectal carcinoma at the oncology unit of Haseki Training and Research Hospital were assessed. The patients for whom EGFR was initiated were examined at the beginning of the treatment at weeks 1 and 2, their demographic characteristics were recorded, and the patients who developed a skin rash were followed up from the onset of the lesion. The PPL side effects that developed in the patients and other dermatological findings were recorded. The PPL side effects were graded, and the treatment plans were reported. The study was conducted between February 2016 and February 2018 under the approval of the local ethical committee. The mean age of the 59 patients (47 females, 12 males) taking EGFR inhibitors was 52.4 ± 12.0 (range: 29–84). Forty-five patients had early stage and 14 patients had advanced stage carcinoma. Fourteen patients had colorectal carcinoma, three patients had renal cancer, and 42 patients had breast cancer. Forty-two patients were using trastuzumab (single therapy in 29 patients and combined therapy in 13 patients), five patients were using cetuximab, three patients were using sunitinib, eight patients were using panitumumab, and six patients were using pertuzumab. In 22 patients, PPL side effects were observed in the skin; it was G1 in 19 patients and G2 in three patients. In seven patients who developed acneiform side effects, systemic doxycycline was used, and in others, topical tetracycline and clindamycin were used. Except for one patient using trastuzumab, all patients has lesions on the face, upper trunk, and back. One patient exhibited an atypical rash, which was diagnosed as a granulomatous follicular reaction. Xerosis was present in two cases, and paronychia, pyogenic granuloma, trichomegaly, and madarosis were observed in one patient each. The patients who developed an acneiform rash were treated with topical and systemic antibiotics, light keratolytics, and emollients. The skin side effects of all patients were mild to moderate, and all patients completed the chemotherapy process. An acneiform skin rash and other dermatological side effects are common with EGFR inhibitors. To treat these side effects, emollients, topical steroids, and local, systemic antibiotics are recommended. Clindamycin may be preferred as a topical treatment, and doxycycline may be preferred as a systematic treatment. [ABSTRACT FROM AUTHOR]

Background: Tyrosine kinase inhibitors (TKIs) are standard treatment options for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Increasing clinical investigations have explored the value of EGFR-TKIs plus antiangiogenic drugs as the first-line treatment for EGFR -mutated NSCLC. Methods: We systematically searched PubMed, Cochrane Library, and EMBASE for randomized controlled trials (RCTs) investigating EGFR-TKIs administered with or without antiangiogenic agents for advanced EGFR -mutated NSCLC. The latest RCT that was presented orally at the 2019 European Society for Medical Oncology Congress was obtained online. The endpoints included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rates (DCRs), and grade 3 or higher adverse events (AEs). Results: We included seven articles on five trials with 1,226 patients. The interventions for the experimental group were the first-generation EGFR-TKI erlotinib combined with bevacizumab (four studies) or ramucirumab (one study), and erlotinib monotherapy (four studies) or erlotinib plus placebo (one study) for the control group. All studies reached their primary study endpoints (i.e., PFS). Compared to erlotinib monotherapy, erlotinib plus antiangiogenic agents remarkably prolonged PFS [hazard ratio (HR) = 0.59, 95% confidence interval (CI) = 0.51–0.69, P = 0.000]; however, ORR, DCR, and OS were similar between the two groups. The overall grade 3–5 AEs increased in combination group (OR = 5.772, 95% CI = 2.38–13.94, P = 0.000), particularly the incidence of diarrhea (OR = 2.51, 95% CI = 1.21–5.23, P = 0.014), acneiform (OR = 1.815, 95% CI = 1.084–3.037, P = 0.023), hypertension (OR = 6.77, 95% CI = 3.62–12.66, P = 0.000), and proteinuria (OR = 13.48, 95% CI = 4.11–44.22, P = 0.000). Additionally, subgroup analysis demonstrated that Asian patients could significantly benefit from combination therapy (HR = 0.59, 95% CI = 0.50–0.69, P = 0.000). Patients with exon 19 deletions (HR = 0.61, 95% CI = 0.49–0.75, P = 0.000) and 21 Leu858Arg mutations (HR = 0.59, 95% CI = 0.47–0.73, P = 0.000) had almost equivalent PFS benefits when treated with double-blocking therapy. Patients with brain metastases at baseline in the combination group had a trend toward better PFS (HR = 0.55, 95% CI = 0.30–1.01, P = 0.001). Conclusions: Erlotinib plus bevacizumab or ramucirumab in EFGR-mutated NSCLC first-line setting yielded remarkable PFS benefits; however, this was accompanied by higher AEs. Epidermal growth factor receptor–TKI plus antiangiogenic agent therapy may be considered a new option for advanced EGFR -mutated NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Patients with locally advanced rectal cancer (LARC) are at higher risk of local and distant recurrence and are thus more vulnerable to metastatic diseases. Neoadjuvant chemoradiotherapy (nCRT) and subsequent curative resection with total mesorectal excision (TME) followed by adjuvant chemotherapy have been recommended by the National Comprehensive Cancer Network (NCCN) guidelines as standard of care for LARC patients. However, the efficacy of the addition of epidermal growth factor receptor (EGFR) inhibitors in kirsten rat sarcoma viral oncogene (KRAS)-wild type LARC patients remains uncertain. Materials: PubMed, Embase, and Web of Science were searched to retrieve records on the application of EGFR inhibitors in a neoadjuvant setting for LARC patients. pCR was used as surrogate endpoint to perform data synthesis in a single-arm setting. Results: Ten cohorts covering 540 subjects were eligible in this systematic review. The pooled pCR rate for EGFR inhibitors was 15% (95% confidence interval (95% CI), 11–20%; I2 = 55.2%); the pooled estimates of Grade 3/4 diarrhea, Grade 3/4 hand–foot syndrome, Grade 3/4 acneiform rash were 17% (95% CI, 4–34%; I2 = 93.3%), 2% (95% CI, 0–5%; I2 = 13.7%), and 15% (95% CI, 9–22%; I2 = 65.4%), respectively. Conclusion: The addition of EGFR inhibitors in the nCRT for KRAS-wild type LARC patients provides comparable efficacy and acceptable safety. However, the results should be interpreted cautiously due to the small amount of relevant data and need further confirmation by more future studies. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor inhibitors (EGFRIs) induced cutaneous toxicity is a common adverse event (AE), although it is not as severe as major cancers, we still need to pay enough attention to them. Therefore, it is necessary to evaluate the diversity of EGFRI class drugs. The objective of this study was to conduct a scientific and systematic investigation into the correlation between EGFRI and cutaneous toxicities. The data accessed from the FDA adverse event reporting system database (FAERS) encompass a time frame spanning from January 2013 to March 2023. By utilizing reporting odds ratios (RORs), information components (ICs), proportional reporting ratios (PRRs), and chi-squared (χ 2 ), the relationship between drugs and adverse reactions was evaluated through disproportionality analysis. Within the FAERS database, a total of 29,559 skin adverse events were recorded. A robust indication of the correlation between EGFRI and elderly patients (≥65 years) was identified. Among EGFRIs, erlotinib accounted for the largest proportion of skin adverse events (39.72%). Rash, dry skin, and pruritus ranked top among all preferred terms, and signals such as rash, skin lesions, and acneiform dermatitis were detected in every single drug. Clinicians should guide patients customize the treatment plan for each patient., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dan, Jiang, Jia, Qi, Zong and Li.)

Background: Papulopustular rash is the most common cutaneous adverse effect during targeted tumour therapy particularly with epidermal growth factor receptor inhibitors (EGFRIs). Objective: To evaluate the adverse skin reactions, mainly papulopustular rash, caused by targeted tumour therapy. Materials and methods: We retrospectively analysed the data of patients who were diagnosed papulopustular rash due to targeted chemotherapeutic agents between January 2016 and August 2018. Demographic characteristics of the patients, the type of malignancy, chemotherapeutic agents causing papulopustular rash, clinical features and grade of the rash, treatment modalities used for the rash, other associated cutaneous adverse reactions, and the need for dose-modification or discontinuation of the chemotherapy were recorded. Results: A total of 39 patients (26 males, 13 females) with a median age of 60 (range 32–86) years were included in the study. EGFRIs such as erlotinib, lapatinib, cetuximab, and panitumumab were the main drugs causing papulopustular rash in 2 (5.1%), 3 (7.6%), 18 (46.1%), and 13 (33.3%) patients, respectively. Imatinib, bevacizumab in combination with oxaliplatin, and everolimus in combination with exemestane and goserelin were responsible in three patients. The most commonly affected area was the face (87.1%) followed by the trunk (56.4%), scalp (25.6%), and extremities (23%). The rash was recorded as grade 1, 2, and 3 in 18, 13, and 6 of the patients, respectively. Grade 3 rash was lead to dose interruptions in 5 (12.8%) patients with subsequent reintroduction at a lower dose in 4 (10.2%) of them and discontinuation of the therapy in 1 (2.5%) patient. Pruritus, xerosis, paronychia, increased growth of the eyelashes, mucositis, hand-foot syndrome (HSF), and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) are other skin toxicities associated with the targeted tumour therapy. Conclusions: With the increasing use of targeted therapies, dermatologists are now confronted with extensive spectrum of skin toxicities. Therefore, it is critical for dermatologists to be aware of these toxicities so as to develop the best approach without discontinuation of cancer therapy. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third leading cause of cancer deaths, and while mortality has largely improved in the developed world, five-year survival for metastatic disease remains dismally low at only 15%. Fortunately, nearly a dozen targeted therapies and immunotherapies have been FDA approved in the past decade for certain patient profiles with metastatic CRC (mCRC), and many others are under development. Checkpoint inhibitors such as pembrolizumab have proven effective at extending survival for mismatch repair (MMR)-deficient and high microsatellite instability (MSI) mCRC patients. In combination with chemotherapy in first- and second-line treatment, antiangiogenic (anti-vascular endothelial growth factor (anti-VGEF)) agent bevacizumab has been shown to increase mCRC survival. Anti-epidermal growth factor receptor (anti-EGFR) agents panitumumab and cetuximab, in combination with chemotherapy, have also prolonged survival among KRAS and all RAS wild-type mCRC patients. Among these patients, anti-EGFR therapy has been found to be more efficacious than bevacizumab. Improved selectivity has allowed small-molecule receptor tyrosine kinase (RTK) inhibitors to target VEGF and EGFR with greater efficacy and tolerability. Combinations of immunotherapies, RTKs, monoclonal antibodies, and cytotoxic drugs are being investigated to provide broad-spectrum protection against relapse by simultaneously targeting many cancer hallmarks. Lastly, human epidermal growth factor receptor 2 (HER2) therapy has shown promise for HER2-positive mCRC patients, though larger clinical trials are required to secure FDA approval. [ABSTRACT FROM AUTHOR]

Background The optimal management of hypomagnesemia (hMg) induced by epidermal growth factor receptor inhibitors (egfris) for advanced colorectal cancer is unclear. We surveyed gastrointestinal medical oncologists in Canada to determine practice patterns for the management of egfri-induced hMg. Methods Based on distribution lists from the Eastern Canadian Colorectal Cancer Consensus Conference and the Western Canadian Gastrointestinal Cancer Consensus Conference, medical oncologists were invited to participate in an online questionnaire between November 2013 and February 2014. Results From the 104 eligible physicians, 40 responses were obtained (38.5%). Panitumumab was more commonly prescribed than cetuximab by 70% of respondents, with 25% prescribing cetuximab and panitumumab equally. Most respondents obtain a serum magnesium level before initiating a patient on an egfri (92.5%) and before every treatment (90%). Most use a reactive strategy for magnesium supplementation (90%) and, when using supplementation, favour intravenous (iv) alone (40%) or iv and oral (45%) dosing. Magnesium sulfate was used for iv replacement, and the most common oral strategies were magnesium oxide (36.4%) and magnesium rougier (18.2%). Under the reactive strategy, intervention occurred at hMg grade 1 (70.3%) or grade 2 (27%). Of the survey respondents, 45% felt that 1-5 of their patients have ever developed symptoms attributable to hMg, and 35% have had to interrupt egfri therapy because of this toxicity, most commonly at grade 3 (30%) or grade 4 (45%) hMg. The most important question about egfri-induced hMg was its relevance to clinical outcomes (45%) and its symptoms (37.5%). Conclusions In Canada, various strategies are used in the management of egfri-induced hMg, including prophylactic and reactive approaches that incorporate iv, oral, or a combination of iv and oral supplementation. Clinicians are concerned about the effect of hMg on clinical outcomes and about the symptoms that patients experience as a result of this toxicity. [ABSTRACT FROM AUTHOR]

Introduction . Epidermal growth factor receptor inhibitors (EGFRI) are commonly used in the treatment of solid tumors. Cutaneous side effects occur in 80% of patients and are the most frequent adverse events. However, cicatricial alopecia is a rarely described side effect of EGFRI. Objective . To present cutaneous toxicities in a patient treated with erlotinib and underscore cicatricial alopecia, rarely described in the literature. Case report. We present a 63-year-old woman diagnosed with non-small cell lung cancer and treated with erlotinib, who developed extensive papulo-pustular eruption with severe involvement of the scalp and cicatricial alopecia. Other adverse events included trichomegaly, paronychia, granuloma pyogenicum-like lesions, dryness of the skin and pruritus. Conclusions . Cicatricial alopecia in the presented patient may be a result of delayed introduction of dermatological treatment. Therefore, all dermatologists should be aware of treatment modalities of EGFRI-induced toxicities.

Colorectal cancer (CRC) is the third leading cause of cancer deaths, and while mortality has largely improved in the developed world, five-year survival for metastatic disease remains dismally low at only 15%. Fortunately, nearly a dozen targeted therapies and immunotherapies have been FDA approved in the past decade for certain patient profiles with metastatic CRC (mCRC), and many others are under development. Checkpoint inhibitors such as pembrolizumab have proven effective at extending survival for mismatch repair (MMR)-deficient and high microsatellite instability (MSI) mCRC patients. In combination with chemotherapy in first- and second-line treatment, antiangiogenic (anti-vascular endothelial growth factor (anti-VGEF)) agent bevacizumab has been shown to increase mCRC survival. Anti-epidermal growth factor receptor (anti-EGFR) agents panitumumab and cetuximab, in combination with chemotherapy, have also prolonged survival among KRAS and all RAS wild-type mCRC patients. Among these patients, anti-EGFR therapy has been found to be more efficacious than bevacizumab. Improved selectivity has allowed small-molecule receptor tyrosine kinase (RTK) inhibitors to target VEGF and EGFR with greater efficacy and tolerability. Combinations of immunotherapies, RTKs, monoclonal antibodies, and cytotoxic drugs are being investigated to provide broad-spectrum protection against relapse by simultaneously targeting many cancer hallmarks. Lastly, human epidermal growth factor receptor 2 (HER2) therapy has shown promise for HER2-positive mCRC patients, though larger clinical trials are required to secure FDA approval.

Introduction: In light of the relevant expenses of pharmacological interventions it might be interesting to make a balance between the cost of the new drugs administered, such as EGFRIs (cetuximab and panitunumab) and the added value represented by the improvement of the clinical parameters of interest such as progression free survival (PFS). Areas covered: The analysis was conducted to assess the effect of front-line chemotherapy on the PFS, separately, on each arm of the evaluated trials. Only phase III randomized controlled trials (RCTs) were considered. We calculated the pharmacological costs necessary to get the benefit in PFS, for each trial. We have subsequently applied the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) to the above phase III RCTs. Our analysis evaluated 9 phase III RCTs, including 7199 patients. ESMO-MCBS reached high scores (grade 4) for the CRYSTAL and PRIME trials. The combination of FOLFOX and panitunumab is associated with low difference per month-PFS gained (15 821.9 €) instead of FOLFIRI plus cetuximab (21 854.6 €) in KRAS wild-type patients. Expert commentary: Our data demonstrate a huge difference in cost per month of PFS gained in modern front-line treatments in mCRC with RAS wild-type. [ABSTRACT FROM AUTHOR]

Antineoplastic targeted therapies, such as EGFR inhibitors, tyrosine kinase inhibitors and BRAF inhibitors, frequently lead to systemic and cutaneous side effects, significantly affecting patient's quality of life. Patients with new targeted therapies have an increased risk of developing skin reactions. The new molecular target therapies developed in the last decades can induce severe skin reactions, which may require dose reduction or discontinuation of treatment and consequently, a decrease in patient's quality of life. The present paper describes toxic cutaneous reactions associated with the most frequently used molecular therapies (epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, BRAF-inhibitors), frequency of occurrence and methods of diagnosis and treatment, in order to offer a clinically efficient management for maintaining a good quality of life, with compliance to treatment and good therapeutic efficacy. Knowledge of cutaneous adverse reactions in new therapies is mandatory in order to have a proper management of oncologic patients. Recognizing target therapy toxicities by both oncologists and dermatologists, understanding therapeutic mechanisms and choosing optimum treatments for oncologic patients are critical. A correct evaluation of skin toxicity can allow for an adequate decision regarding treatment dose or discontinuation, impacting therapy response and patient survival. [ABSTRACT FROM AUTHOR]

In modern drug discovery, virtual screening is an attractive and cost-effective approach, which is widely applied to filter chemical compound libraries for the identification of novel inhibitors. Epidermal growth factor receptor protein is a well reported anticancer molecular target due to its over expression and mutation in many solid tumours. The decline in epidermal growth factor receptor activity by small molecules has proved to be an effective treatment for cancer. To design inhibitors for this target, the crystal structures information of epidermal growth factor receptors, co-crystallized with its inhibitors, provide a gateway to perform receptor-based drug designing studies, whereas the inhibitors with their biological activity reported in literature provide information to carry out ligand-based drug designing studies. In the present study, the drug designing methods were strategically combined and used parallely on a library of 50,000 drug-like compounds from ChemDiv and ChemBridge database, for the selection of potential inhibitors of epidermal growth factor receptor. This resulted in the identification of 200 common hits, which were further pruned down to 87, based on the knowledge about the key interaction of known epidermal growth factor receptor inhibitors with Met793. These 87 hits were clustered into 12 different structural moieties. In vitro studies of some of these hits were also carried out in order to validate the screening approach. Further, the lead optimization studies were performed by analyzing the binding poses of all the identified structural moieties in order to ascertain the scope of modifications around these moieties. Molecular dynamics simulation studies further revealed some important residues of the target which may be helpful for providing stability to the enzyme-inhibitor complex. These findings could be very much helpful for a medicinal chemist to design a novel potent inhibitor of epidermal growth factor receptor. [ABSTRACT FROM AUTHOR]

The majority of patients with head and neck cancer present with locally advanced disease. Locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) poses one of the most complex management challenges. This stage of disease is still potentially curable, but requires combined-modality therapy. One of the novel approaches is the use of targeted agents, particularly the epidermal growth factor receptor (EGFR) inhibitors, in treatment strategies in LA-SCCHN. A Medline search covering topics related to targeted therapies in head and neck cancer over the last two decades was made and the facts were compiled. Cetuximab was the first novel agent to obtain regulatory approval in the United States for the treatment of patients with Head and Neck Squamous Cell Cancer HNSCC. Cetuximab has been evaluated in combination with radiotherapy, chemo-radiotherapy, and induction chemotherapies, and was found to increase the overall survival rates in all the arms without raising the toxicity level of the combined modality of treatment significantly. The tyrosine kinase inhibitors Gefinitib and Erlotinib also produced an average response rate of 11% and 4% in different studies and also prolonged the disease control rates when used with chemotherapy. This paper will review the role of targeted agents, particularly the EGFR inhibitors, in the present treatment strategies in advanced, recurrent/metastatic head and neck cancer.

Over the past decades, considerable progress has been made in the management of colorectal cancer (CRC), leading to a significant improvement in overall survival. Although part of this success has been rightly attributed to aggressive surgical management and advances in other adjunct treatments, our understanding of the pathogenesis of CRC and emergence of newer molecular targets for colon cancer has created a powerful impact. In this review article, we will discuss various targeted therapies in the management of metastatic CRC (mCRC). In particular, vascular endothelial growth factor (VEGF)- and epidermal growth factor receptor (EGFR)-targeting monoclonal antibodies have become integral components of the first-line treatment strategies for mCRC. Newer agents on the horizon soon to be incorporated in clinical practice will be briefly reviewed as well. Currently, the only predictive biomarker for treatment selection in patients with mCRC is tumor RAS mutational status. [ABSTRACT FROM AUTHOR]

Purpose: Epidermal growth factor receptor inhibitors such as panitumumab are associated with characteristic skin toxicities. We summarise data from three panitumumab clinical trials to investigate the potential impact of skin toxicity on quality of life (QoL) in patients with metastatic colorectal cancer (mCRC).Methods: The studies were randomised, open-label trials comparing standard treatment (first-line FOLFOX4 [n = 456], second-line FOLFIRI [n = 381], or best supportive care [n = 114]) with or without panitumumab in adults with KRAS/NRAS (RAS) wild-type mCRC. QoL was assessed using the EuroQoL 5-domain health state index (HSI) and overall health rating (OHR) measures. Impact of skin toxicity on changes in QoL scores was estimated using a linear mixed-effects model. Worst skin toxicity was defined in separate models as a subgroup variable or as a measure over time.Results: Regardless of analysis method, there were no statistically significant differences between the panitumumab and comparator arms in any of the studies in terms of change in HSI or OHR scores. There were no statistically significant differences in QoL outcomes between patients with worst skin toxicity grade <3 and those with grade ≥3. In addition, there were no statistically significant differences between the panitumumab and comparator arms in subgroups of patients with worst skin toxicity of grade <3 and ≥3.Conclusions: Addition of panitumumab to chemotherapy in RAS wild-type mCRC has no statistically significant negative effect on overall QoL, despite skin toxicity. Skin toxicity of worst grade ≥3 appeared to have similar impact on QoL as skin toxicity of grade <3. [ABSTRACT FROM AUTHOR]

Wprowadzenie: Inhibitory receptora naskórkowego czynnika wzrostu (ang. epidermal growth factor receptor inhibitors - EGFRI) są coraz częściej stosowane w leczeniu guzów litych. Skórne działania niepożądane, występujące u ponad 80% pacjentów, należą do najczęstszych powikłań terapii. W piśmiennictwie istnieją jedynie pojedyncze opisy łysienia bliznowaciejącego u pacjentów leczonych EGFRI. Cel pracy: Przedstawienie i omówienie skórnych działań niepożądanych EGFRI ze szczególnym zwróceniem uwagi na rzadko opisywane łysienie bliznowaciejące. Opis przypadku: Przedstawiamy 63-letnią kobietę z rakiem gruczołowym płuca lewego leczonym EGFRI (erlotynibem), u której wystąpiły rozsiane zmiany grudkowo-krostkowe, najbardziej nasilone na skórze głowy, z towarzyszącym łysieniem bliznowaciejącym. Ponadto obecne były: trichomegalia, zapalenie wałów paznokciowych ze zmianami przypominającymi ziarniniaki naczyniowe, suchość i świąd skóry. W wyniku zastosowanej ogólnie antybiotykoterapii i leczenia miejscowego ustąpiły wykwity krostkowe. Wnioski: Rozległe łysienie bliznowaciejące u przedstawionej pacjentki może być następstwem późnego rozpoczęcia leczenia dermatologicznego. Dermatolodzy powinni być świadomi zagrożeń związanych ze stosowaniem leków z grupy EGFRI. Introduction: Epidermal growth factor receptor inhibitors (EGFRI) are commonly used in the treatment of solid tumors. Cutaneous side effects occur in 80% of patients and are the most frequent adverse events. However, cicatricial alopecia is a rarely described side effect of EGFRI. Objective: To present cutaneous toxicities in a patient treated with erlotinib and underscore cicatricial alopecia, rarely described in the literature. Case report: We present a 63-year-old woman diagnosed with non-small cell lung cancer and treated with erlotinib, who developed extensive papulo-pustular eruption with severe involvement of the scalp and cicatricial alopecia. Other adverse events included trichomegaly, paronychia, granuloma pyogenicum-like lesions, dryness of the skin and pruritus. Conclusions: Cicatricial alopecia in the presented patient may be a result of delayed introduction of dermatological treatment. Therefore, all dermatologists should be aware of treatment modalities of EGFRI-induced toxicities. [ABSTRACT FROM AUTHOR]

Background Erythematous papulopustular eruption ( EPPE) is the most frequent skin adverse event to epidermal growth factor receptor ( EGFR) inhibitors but its histopathologic features have been poorly studied. As EPPE is a strong predictor of patient's treatment response, the EPPE histopathologic features and their correlations with skin eruption severity and involved drug were investigated. Method An involved skin biopsy was carried out in 39 informed patients treated with EGFR inhibitors (mainly cetuximab and erlotinib). The cutaneous changes in hematoxylin-eosin stained sections were evaluated. Results The EPPE to EGFR inhibitors is histopathologically characterized by neutrophilic subcorneal or intraepidermal pustules and polymorphous infiltrate of the superficial dermis during the earliest phases and by lymphocytic perifolliculitis and/or suppurative folliculitis at a later phase. The widespread dermis inflammation was more frequent in severe EPPEs and in patients treated with cetuximab, while the hair follicle inflammation was observed only in mild/moderate EPPEs. Conclusion Our study shows the histopathologic signs of EPPE and their correlation with clinical severity and the offending drug. [ABSTRACT FROM AUTHOR]