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BMC Cancer Mar 2021Lung cancer is most common among older individuals. However, polypharmacy and comorbidities, which are also more common in older individuals, can limit treatment...
A phase II study of first-line afatinib for patients aged ≥75 years with EGFR mutation-positive advanced non-small cell lung cancer: North East Japan Study Group trial NEJ027.
BACKGROUND
Lung cancer is most common among older individuals. However, polypharmacy and comorbidities, which are also more common in older individuals, can limit treatment options. Previous studies suggest that afatinib can be used safely and effectively in elderly patients. This study investigated the anti-tumour activity and safety profile of first-line afatinib in previously-untreated elderly Japanese patients with EGFR mutation-positive non-small cell lung cancer (NSCLC).
METHODS
This was a single-arm, open-label, phase II study, performed in multiple centres in Japan. Previously untreated patients, aged ≥75 years, with EGFR mutation-positive (Del19 or L858R) advanced NSCLC were treated with afatinib 40 mg until disease progression or unacceptable toxicity. Adverse events (AEs) were managed with protocol-defined dose adjustments. The primary endpoint was objective response rate (ORR) by central review.
RESULTS
In total, 38 patients received at least one dose of afatinib, and 37 were evaluable for response. Median age was 77.5 years (range 75-91), all patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, and 60.5% had Del19-positive disease. Median follow-up was 838 days. ORR was 75.7% (2 complete responses and 26 partial responses). Median progression-free survival was 14.2 months (95% confidence interval [CI], 9.5-19.0). Median overall survival (OS) was 35.2 months (95% CI, 35.2-not reached); the 2-year OS rate was 78.3%. The most common grade 3/4 treatment-related AEs (TRAEs) were diarrhoea (28.9%), paronychia (23.7%), and rash/acne (15.8%). Dose reductions due to TRAEs were reported in 78.9% of patients, and eight (21.1%) patients discontinued afatinib due to TRAEs. No treatment-related deaths were reported.
CONCLUSION
Although dose adjustments were relatively common in this small group of Japanese patients aged ≥75 years with EGFR mutation-positive NSCLC, discontinuation occurred much less frequently, and most patients were able to stay on treatment for well over a year. Further, afatinib was associated with high response rates and prolonged PFS and OS.
TRIAL REGISTRATION
The trial is registered with Japan Registry of Clinical Trials (JRCT) as trial number 031180136 (date of initial registration: 19 February 2019), and the University Hospital Network (UMIN) as trial number 000017877 (date of initial registration: 11 June 2015).
Topics: Afatinib; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Dose-Response Relationship, Drug; ErbB Receptors; Female; Gastrointestinal Diseases; Humans; Japan; Kaplan-Meier Estimate; Lung Neoplasms; Male; Neoplasm Proteins; Progression-Free Survival; Protein Kinase Inhibitors; Skin Diseases
PubMed: 33648453
DOI: 10.1186/s12885-021-07861-1 -
Frontiers in Pharmacology 2021As one of the second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, afatinib brings survival benefits to patients with common and rare... (Review)
Review
As one of the second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, afatinib brings survival benefits to patients with common and rare EGFR mutations. This study aimed to compare the effectiveness and safety of 30 and 40 mg of afatinib in patients with non-small cell lung cancer (NSCLC) using qualitative and quantitative analysis methods so as to provide reference for clinical medication. The PubMed, Embase, ClinicalTrials.gov, Cochrane Library, China National Knowledge Infrastructure, and WanFang databases were thoroughly searched from inception to February 26, 2021. Two researchers independently screened the literature, extracted data, and evaluated the quality. RevMan and Stata 15.0 were used for meta-analysis. Twelve cohort studies including 1290 patients for final analysis were selected; of which, 1129 patients were analyzed to measure the effectiveness outcomes and 470 patients were analyzed for safety outcomes. In patients with non-brain metastasis, the progression-free survival of the first- or second-line treatment with reduced-dose afatinib was equivalent to the conventional dose. In terms of safety, the reduced dose could significantly lower the incidence of severe diarrhea and severe rash, but not the total incidence of diarrhea, rash, and all levels of paronychia. The incidence of common serious adverse reactions was significantly lower with 30 mg of afatinib than with 40 mg of afatinib in patients with NSCLC. The effectiveness appeared to be similar to that in patients with non-brain metastasis. This study provides a reference for clinical dose reduction of afatinib. [PROSPERO], identifier [CRD42021238043].
PubMed: 34912228
DOI: 10.3389/fphar.2021.781084 -
Cureus Apr 2023Pemphigus vulgaris (PV) is a rare disease that affects the skin and mucous membranes, causing blistering and erosions. Identifying and effectively managing atypical...
Pemphigus vulgaris (PV) is a rare disease that affects the skin and mucous membranes, causing blistering and erosions. Identifying and effectively managing atypical presentations of pemphigus vulgaris can be challenging due to its rarity. We describe a 32-year-old male patient with a medical history including prediabetes, moderate asthma, hyperlipidemia, coccidioidomycosis, and respiratory infections. He was evaluated via telehealth in the allergy and immunology clinic for uncontrolled asthma. Initially, he complained of a whitish film in the mouth while on treatment with fluticasone and salmeterol. He also noted new vesicular lesions on his scalp and body. When evaluated later in the clinic, he was found to have oral and periungual erosions as well as paronychia. After promptly referring to dermatology, histopathological examination and direct immunofluorescence testing were performed on the patient's lesions, revealing changes consistent with PV. Treatment with prednisone and rituximab resulted in the complete resolution of the patient's bullae and nail deformities over several months. This case highlights the importance of a thorough evaluation of complex medical histories and diagnostic testing in managing asthma and allergy symptoms. It also emphasizes the need for a multidisciplinary approach involving specialists such as immunologists, dermatologists, and infectious disease experts in the diagnosis and management of complex cases.
PubMed: 37261177
DOI: 10.7759/cureus.38334 -
Indian Dermatology Online Journal 2020Onychopathies or nail disorders are associated with social stigma and causes limitation of daily activities by hampering the function of both fingers and toes.
BACKGROUND
Onychopathies or nail disorders are associated with social stigma and causes limitation of daily activities by hampering the function of both fingers and toes.
AIM
To evaluate the impact of onychopathies on quality of life (QoL) and compare the severity of impact on QoL in various nail disorders.
MATERIALS AND METHODS
A hospital-based cross-sectional study consisting of 540 patients with onychopathies was conducted in the dermatology outpatient department. Patients were requested to complete a nail-specific QoL questionnaire consisting of 24 and 16 questions, respectively, for fingernails (group F) and toenails (group T) with five possible responses to each question. A score of 1-5 was given to each response. Statistical analysis was done to compare the impact of QoL on the different types of onychopathies.
RESULTS
We found that onychopathies have a significant impact on QoL. QoL was significantly more affected when multiple nails were involved ( = 0.020 for group F and = 0.001 for group T). QoL impact was statistically more significant in women ( = 0.038 for group F and < 0.001 for group T) and in younger people aged <20 years in group F and 20-39 years in group T ( < 0.001 for both groups F and T). Patients with onychomycosis, structural nail defects, and psoriasis had a more significant impact than other diseases ( < 0.001 for both groups F and T).
CONCLUSION
Onychopathies have a significant adverse effect on QoL because of their serious physical, psychological and social impact. Hence, clinicians should treat the nail disorders with utmost seriousness.
PubMed: 32477977
DOI: 10.4103/idoj.IDOJ_272_19 -
Skin Appendage Disorders Nov 2022Cuticle reduction and removal techniques are commonly performed by nail technicians for nail cosmesis. However, manipulation of the nail cuticle can lead to localized...
INTRODUCTION
Cuticle reduction and removal techniques are commonly performed by nail technicians for nail cosmesis. However, manipulation of the nail cuticle can lead to localized infection and nail dystrophy.
CASE PRESENTATION
In this case, a 20-year-old woman from the Philadelphia area in the USA presented with onychomadesis secondary to acute paronychia following a "Russian" manicure. In this technique, an electronic filer is used to completely remove the cuticle, leaving the proximal nail fold exposed and vulnerable.
CONCLUSION
As this style of manicure is being inaccurately publicized as safe, it is important that dermatologists are aware of this technique and educate our patients about its potential for harm.
PubMed: 36407651
DOI: 10.1159/000525023 -
Cancers Oct 2023Epidermal growth factor receptor () T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second...
A Phase II Study of Osimertinib in Patients with Advanced-Stage Non-Small Cell Lung Cancer following Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Therapy with EGFR and T790M Mutations Detected in Plasma Circulating Tumour DNA (PLASMA Study).
Epidermal growth factor receptor () T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second generation (1G/2G) EGFR tyrosine kinase inhibitors (TKIs) and are sensitive to Osimertinib. Tissue sampling is the gold-standard modality of T790M testing, but it is invasive. We evaluated the efficacy of Osimertinib in patients with EGFR mutant NSCLC and T790M in circulating tumour DNA (ctDNA). PLASMA is a prospective, open-label, multicentre single-arm Phase II study. Patients with advanced NSCLC harbouring sensitizing EGFR and T790M mutations in plasma at progression from ≥one 1G/2G TKI were treated with 80 mg of Osimertinib daily until progression. The primary endpoint was the objective response rate (ORR); the secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and toxicities. Plasma next-generation sequencing was performed to determine Osimertinib resistance mechanisms and assess serial ctDNA. A total of 110 patients from eight centres in five countries were enrolled from 2017 to 2019. The median follow-up duration was 2.64 (IQR 2.44-3.12) years. The ORR was 50.9% (95% CI 41.2-60.6) and the DCR was 84.5% (95% CI 76.4-90.7). Median PFS was 7.4 (95% CI 6.0-9.3) months; median OS was 1.63 (95% CI 1.35-2.16) years. Of all of the patients, 76% had treatment-related adverse events (TRAEs), most commonly paronychia (22.7%); 11% experienced ≥ Grade 3 TRAEs. The ctDNA baseline load and dynamics were prognostic. Osimertinib is active in NSCLC harbouring sensitizing EGFR and T790M mutations in ctDNA testing post 1G/2G TKIs.
PubMed: 37894366
DOI: 10.3390/cancers15204999 -
Plants (Basel, Switzerland) Nov 2021The widespread use of chemical control agents and pesticides for plant-pathogen control has caused many human health and environmental issues. Plant extracts and...
The widespread use of chemical control agents and pesticides for plant-pathogen control has caused many human health and environmental issues. Plant extracts and biocontrol agents have robust antimicrobial activity against different plant pathogens. However, their antiviral activities are still being investigated. In the present study, the methanol extract of was characterized and evaluated for its protective activity against the tobacco mosaic virus (TMV) infection in tomato plants under greenhouse conditions at 21 days post-inoculation. The results showed that the foliar application of extract (10 µg/mL) enhanced tomato plant growth, resulting in significant increases in shoot and root parameters and total chlorophyll contents. Moreover, a significant reduction in TMV accumulation level in -treated plants of 77.88% compared to non-treated plants was reported. Furthermore, induction of systemic resistance with significant elevation in production of antioxidant enzymes (PPO, CAT, and SOD) and transcriptional levels of the pathogenesis-related proteins (PR-1 and PR-7) and polyphenolic genes (CHS and HQT) were also observed. Out of 16 detected compounds, HPLC analysis revealed that the most abundant polyphenolic compounds found in extract were gallic acid (5.36 µg/mL), kaempferol (7.39 µg/mL), quercetin (7.44 µg/mL), ellagic acid (7.89 µg/mL), myricetin (8.36 µg/mL), and ferulic acid (8.69 µg/mL). The findings suggest that the use of extract as an effective and safe source for the production of bioactive compounds may offer a solution for a promising approach for the management of plant viral infections. To the best of our knowledge, this is the first report of the protective activity of extract against plant viral diseases.
PubMed: 34834798
DOI: 10.3390/plants10112435 -
Indian Journal of Dermatology 2020
PubMed: 32565575
DOI: 10.4103/ijd.IJD_348_18 -
Cancer Management and Research 2021The clinical outcomes of elderly patients with -mutated non-small cell lung cancer (NSCLC) who are treated with osimertinib have not been sufficiently evaluated. This...
BACKGROUND
The clinical outcomes of elderly patients with -mutated non-small cell lung cancer (NSCLC) who are treated with osimertinib have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in elderly chemotherapy-naive patients with NSCLC harboring sensitive mutations.
PATIENTS AND METHODS
We assessed the clinical effects of osimertinib as a first-line treatment for elderly NSCLC patients (≥75 years of age) with an exon 19 deletion or exon 21 L858R mutation in . All patients were administered 80 mg/day osimertinib as initial treatment.
RESULTS
Forty-three patients (24 women and 19 men) with adenocarcinoma who were treated between August 2018 and July 2021 were included in this study; their median age was 79 years (range, 75-90 years). The overall objective response rate was 60.5%. The median progression-free survival (PFS) and time to treatment failure (TTF) of the entire patient population were 22.1 months and 14.6 months, respectively. The most common adverse event was rash acneiform (42%), followed by diarrhea (33%) and paronychia (28%); none of these were grades ≥3. Interstitial lung disease developed in 8 patients (18.6%); however, no treatment-related deaths occurred. Multivariate analysis identified performance status and disease stage as predictors of PFS and TTF.
CONCLUSION
Considering the findings of this study and despite an observed discordance between PFS and TTF, osimertinib appears to be an effective and safe treatment option in elderly patients with advanced NSCLC harboring sensitive mutations. To obtain conclusive results, further studies in a larger elderly population are warranted.
PubMed: 34849025
DOI: 10.2147/CMAR.S339891 -
Cancer Medicine Apr 2024Long-term anti-EGFR antibody treatment increases the risk of severe dermatologic toxicities. This single-arm, phase II trial aimed to investigate the strategy of...
BACKGROUND
Long-term anti-EGFR antibody treatment increases the risk of severe dermatologic toxicities. This single-arm, phase II trial aimed to investigate the strategy of switching from cetuximab to bevacizumab in combination with FOLFIRI based on early tumor shrinkage (ETS) in patients with RAS wild-type metastatic colorectal cancer (mCRC).
METHODS
Radiologic assessment was performed to evaluate ETS, defined as ≥20% reduction in the sum of the largest diameters of target lesions 8 weeks after the introduction of FOLFIRI plus cetuximab. ETS-negative patients switched to FOLFIRI plus bevacizumab, whereas ETS-positive patients continued FOLFIRI plus cetuximab for eight more weeks, with a switch to FOLFIRI plus bevacizumab thereafter. The primary endpoint was progression-free survival.
RESULTS
This trial was prematurely terminated due to poor accrual after a total enrollment of 30 patients. In 29 eligible patients, 7 were ETS-negative and 22 were ETS-positive. Two ETS-negative patients and 17 ETS-positive patients switched to FOLFIRI plus bevacizumab 8 weeks and 16 weeks after initial FOLFIRI plus cetuximab, respectively. Median progression-free and overall survival durations were 13.4 and 34.7 months, respectively. Six (20%) patients experienced grade ≥3 paronychia, which improved to grade ≤2 by 18 weeks. Grade ≥3 acneiform rash, dry skin, and pruritus were not observed in any patients.
CONCLUSIONS
Our novel treatment strategy delivered acceptable survival outcomes and reduced severe dermatologic toxicities.
Topics: Humans; Bevacizumab; Cetuximab; Colorectal Neoplasms; Camptothecin; Fluorouracil; Colonic Neoplasms; Rectal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Leucovorin
PubMed: 38591098
DOI: 10.1002/cam4.7107