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Cancer Medicine Jul 2023Dacomitinib significantly improves progression-free survival and overall survival (OS) compared with gefitinib in patients with non-small-cell lung cancer (NSCLC)...
BACKGROUND
Dacomitinib significantly improves progression-free survival and overall survival (OS) compared with gefitinib in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-activating mutations. However, dacomitinib often causes skin toxicities, resulting in treatment discontinuation. We aimed to evaluate a prophylactic strategy for skin toxicity induced by dacomitinib.
METHODS
We performed a single-arm, prospective, open-label, multi-institutional phase II trial for comprehensive skin toxicity prophylaxis. Patients with NSCLC harboring EGFR-activating mutations were enrolled and received dacomitinib with comprehensive prophylaxis. The primary endpoint was the incidence of skin toxicity (Grade ≥2) in the initial 8 weeks.
RESULTS
In total, 41 Japanese patients participated between May 2019 and April 2021 from 14 institutions (median age 70 years; range: 32-83 years), 20 were male, and 36 had a performance status of 0-1. Nineteen patients had exon 19 deletions and L858R mutation. More than 90% of patients were perfectly compliant with prophylactic minocycline administration. Skin toxicities (Grade ≥2) occurred in 43.9% of patients (90% confidence interval [CI], 31.2%-56.7%). The most frequent skin toxicity was acneiform rash in 11 patients (26.8%), followed by paronychia in five patients (12.2%). Due to skin toxicities, eight patients (19.5%) received reduced doses of dacomitinib. The median progression-free survival was 6.8 months (95% CI, 4.0-8.6 months) and median OS was 21.6 months (95% CI, 17.0 months-not reached).
CONCLUSION
Although the prophylactic strategy was ineffective, the adherence to prophylactic medication was quite good. Patient education regarding prophylaxis is important and can lead to improved treatment continuity.
Topics: Humans; Male; Aged; Female; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Prospective Studies; Protein Kinase Inhibitors; ErbB Receptors; Mutation
PubMed: 37269194
DOI: 10.1002/cam4.6184 -
Pharmaceuticals (Basel, Switzerland) Jul 2022Trametinib has been used in neurofibromatosis type 1 (NF1) patients, especially those with unresectable nerve tumors, but no systematic review based on the latest... (Review)
Review
Trametinib has been used in neurofibromatosis type 1 (NF1) patients, especially those with unresectable nerve tumors, but no systematic review based on the latest studies has been published. We conducted this meta-analysis to evaluate the effectiveness and safety of trametinib in treating NF1-related nerve tumors. Original articles reporting the efficacy and safety of trametinib in NF1 patents were identified in PubMed, EMBASE, and Web of Science up to 1 June 2022. Using R software and the 'meta' package, the objective response rates (ORRs) and disease control rates (DCRs) were calculated to evaluate the efficacy, and the pooled proportion of adverse events (AEs) was calculated. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. Eight studies involving 92 patients were included, which had a very low to moderate quality of evidence. The pooled ORR was 45.3% (95% CI: 28.9-62.1%, I = 0%), and the DCR was 99.8% (95% CI: 95.5-100%, I = 0%). The most common AEs was paronychia, with a pooled rate of 60.7% (95% CI: 48.8-72.7%, I = 0%). Our results indicate the satisfactory ability to stabilize tumor progression but a more limited ability to shrink tumors of trametinib in NF1-related nerve tumors. The safety profile of trametinib is satisfactory.
PubMed: 36015104
DOI: 10.3390/ph15080956 -
Asian Pacific Journal of Cancer... May 2021We aimed to evaluate the effectiveness and tolerability of Afatinib as first-line treatment of advanced epidermal growth factor receptor (EGFR) mutant non small cell...
BACKGROUND
We aimed to evaluate the effectiveness and tolerability of Afatinib as first-line treatment of advanced epidermal growth factor receptor (EGFR) mutant non small cell lung cancer (NSCLC) in a real-world setting.
PATIENTS AND METHODS
This is a retrospective study of Vietnamese patients with advanced EGFR-mutant NSCLC treated with first-line afatinib at the National Cancer Hospital from 1st January 2018 to 31st October 2020. Patients' demographic, clinical and treatment data were captured. Objective response rate (ORR), disease control rate (DCR), time to treatment failure (TTF) and tolerability were evaluated. We used Kaplan-Meier curve and log-rank test for survival, and Cox regression model for multivariate analysis.
RESULTS
A total of 44 patients were included. Common EGFR mutations (Del 19/L858R) were detected in 61% patients. Fifty percent of patients with uncommon mutations had compound mutations of G719X, L861Q and S768I. The ORR was 75% while DCR rate was 98%. The median TTF was 12.3 months (95% CI: 7.2-17.3); the mTTFs were 12.3 and 10.8 months for patients with common and uncommon mutations (p = 0.001), respectively, and 14.0 and 7.5 months for patients with Del 19 and L858R mutations (p = 0.067), respectively. Afatinib 30 mg once daily was the most common starting (77%) and maintenance (64%) doses. The mTTFs were 12.3 and 7.5 months for patients with 30 mg starting dose vs 40 mg dose (p = 0.256), respectively. Diarrhea, skin rash, paronychia and fatigue were observed in 32%, 30%, 25% and 9%, respectively. There was no grade 4 toxicity except three patients with grade 3 paronychia.
CONCLUSIONS
First-line afatinib is beneficial for Vietnamese patients with advanced EGFR-mutant NSCLC with a good response rate and prolonged TTF with manageable adverse event profile. Baseline brain metastasis status and starting doses do not significantly impact TTF.
.Topics: Adult; Afatinib; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Mutation; Prognosis; Retrospective Studies; Survival Rate
PubMed: 34048189
DOI: 10.31557/APJCP.2021.22.5.1581 -
Journal of the American Academy of... Sep 2000Nail involvement in pemphigus vulgaris is relatively rare. We describe a case of severe pemphigus involving both the skin and oral mucosa in which an acute exacerbation... (Review)
Review
Nail involvement in pemphigus vulgaris is relatively rare. We describe a case of severe pemphigus involving both the skin and oral mucosa in which an acute exacerbation was preceded by the onset of nail involvement of all 4 extremities. Nail involvement occurred in the form of hemorrhagic paronychia of multiple digits. Oral, cutaneous, and nail manifestations of the disease were all well controlled by systemic therapy. A review of the literature on nail involvement in pemphigus reveals that this involvement may be manifested in multiple ways, with chronic paronychia and onychomadesis being the most common. Involvement of the nail occurs most frequently either as part of the initial presentation, or just before or concurrent with a flare of pre-existing disease. Nail involvement, when it occurs, is usually present when the disease is severe. Topical therapy is insufficient, and systemic therapy is warranted. In the majority of cases, nail recovery is complete, with no residual damage.
Topics: Foot; Hand; Humans; Immunoglobulins, Intravenous; Infusions, Intravenous; Male; Middle Aged; Nail Diseases; Pemphigus; Recurrence
PubMed: 10954669
DOI: 10.1067/mjd.2000.106236 -
Frontiers in Oncology 2022Epidermal growth factor receptor (EGFR) inhibitors are widely used to treat various types of cancers such as non-small cell lung cancer, head and neck cancer, breast... (Review)
Review
Epidermal growth factor receptor (EGFR) inhibitors are widely used to treat various types of cancers such as non-small cell lung cancer, head and neck cancer, breast cancer, pancreatic cancer. Adverse reactions such as skin toxicity, interstitial lung disease, hepatotoxicity, ocular toxicity, hypomagnesemia, stomatitis, and diarrhea may occur during treatment. Because the EGFR signaling pathway is important for maintaining normal physiological skin function. Adverse skin reactions occurred in up to 90% of cancer patients treated with EGFR inhibitors, including common skin toxicities (such as papulopustular exanthemas, paronychia, hair changes) and rare fatal skin toxicities (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis). This has led to the dose reduction or discontinuation of EGFR inhibitors in the treatment of cancer. Recently, progress has been made about research on the skin toxicity of EGFR inhibitors. Here, we summarize the mechanism of skin toxicity caused by EGFR inhibitors, measures to prevent severe fatal skin toxicity, and provide reference for medical staff how to give care and treatment after adverse skin reactions.
PubMed: 35223483
DOI: 10.3389/fonc.2022.804212 -
Skin Appendage Disorders Nov 2022Symptoms of pemphigus vulgaris (PV) rarely include nail findings. When ungual involvement does occur, the most common manifestations are paronychia and onychomadesis....
INTRODUCTION
Symptoms of pemphigus vulgaris (PV) rarely include nail findings. When ungual involvement does occur, the most common manifestations are paronychia and onychomadesis. Onycholysis is very uncommon, and complete nail loss has not been reported in the literature. Ungual involvement is thought to be closely correlated with disease severity, with only severe PV cases demonstrating nail symptoms.
CASE PRESENTATION
We report a case of a 34-year-old female presenting with mild to moderate PV yet severe onycholysis of her first toe leading to secondary nail loss in conjunction with paronychia of her bilateral thumbs. Oral tofacitinib and rituximab infusions led to strikingly rapid improvement in her nail symptoms.
DISCUSSION/CONCLUSION
This case illustrates the importance of a thorough history and physical exam, as a primary complaint of nail symptoms in these patients may lead to unrecognized PV by even the most skilled practitioners. Tofacitinib and rituximab in combination may rapidly improve nail involvement.
PubMed: 36407650
DOI: 10.1159/000525462 -
Skin Appendage Disorders Aug 2023Onychogryphosis is a nail condition characterized clinically by a thickened, curved, yellow-brown, and opaque nail plate and may result in pain, paronychia, and...
INTRODUCTION
Onychogryphosis is a nail condition characterized clinically by a thickened, curved, yellow-brown, and opaque nail plate and may result in pain, paronychia, and onychogryphosis.
METHODS
We performed a nested case-control study of 1,114 onychogryphosis patients and 3,423 matched controls to quantify the association between onychogryphosis and self-care limitations, chronic foot injury, dermatologic conditions, and vascular disease.
RESULTS AND CONCLUSION
Onychogryphosis was positively associated with increased age, activity limitations (difficulty running errands alone, bathing, and concentrating), psoriasis, onychomycosis, hallux malleus, hallux valgus, peripheral vascular disease, lower extremity ulcers, venous varices, and type II diabetes mellitus. Therefore, physicians should screen patients presenting with onychogryphosis for these conditions.
PubMed: 37564683
DOI: 10.1159/000530096 -
Actas Dermo-sifiliograficas May 2012Leprosy, a disease caused by Mycobacterium leprae, primarily affects the skin and nerves, but the nails are also involved in as many as 3 out of 4 patients .The factors... (Review)
Review
Leprosy, a disease caused by Mycobacterium leprae, primarily affects the skin and nerves, but the nails are also involved in as many as 3 out of 4 patients .The factors that trigger nail changes in leprosy are numerous and include repeated trauma, neuropathy, vascular impairment, infections, lepra reactions, and the drugs used to manage the disease. The changes most often reported include subungual hematomas, onycholysis, onychauxis, onychogryphosis, pterygium unguis, and onychoheterotopia, most of which can be attributed to nerve damage and trauma. Furthermore, the acro-osteolysis that occurs in the advanced stages of the disease may present with brachyonychia, racquet nails, or even anonychia. Infections of the nail bed leading to paronychia and onychomycosis should also be taken into account in leprosy. Other typical changes include longitudinal striae, pitting, macrolunula, Terry nails, leukonychia, hapalonychia, and Beau lines. In this review, we describe the principal nail changes associated with leprosy. These changes, which are highly varied and diverse in origin, are in fact a reflection of the significant morbidity caused by M. leprae infection.
Topics: Humans; Leprosy; Nail Diseases
PubMed: 22056258
DOI: 10.1016/j.ad.2011.07.011 -
Nihon Ishinkin Gakkai Zasshi = Japanese... 2009This document summarizes current knowledge about diagnosis and treatment of candidiasis affecting the skin and oral mucosa. Several clinical forms of mucocutaneous... (Review)
Review
This document summarizes current knowledge about diagnosis and treatment of candidiasis affecting the skin and oral mucosa. Several clinical forms of mucocutaneous candidiasis are distinguished depending on a patient's age and infected site, e.g. Candida intertrigo, erythema mycoticum infantile, erosio interdigitalis blastomycetica, candidal paronychia and onychia, Candida onychomycosis, and oral candidiasis. The diagnosis of candidiasis is confirmed by observation of mycelial forms on microscopic examination. Since Candida yeasts (especially C. albicans) are normal inhabitants of the skin and oral mucosa, it must always be noted that positive culture does not always indicate the presence of candidal infection. The pathogenicity of Candida species is relatively low, and some special conditions are required for tissue invasion by the fungus. Predisposing factors, such as disturbances of the cutaneous and mucosal microenvironment and systemic or local immunosuppression, should be checked in patients with recurrent infection. Therapy for cutaneous candidiasis is dominated by topical antifungal agents. Azole antifungal cream (e.g., bifonazole, ketoconazole, neticonazole hydrochloride, lanoconazole and luliconazole) is most effective. Terbinafine hydrochloride and amorolfine hydrochloride are also useful. Cutaneous candidiasis usually requires a shorter duration of topical treatment (1-2 weeks) than superficial dermatophyte infections. For candidal paronychia and onychomycosis, oral therapy with itraconazole is recommended. The daily dose of itraconazole should be taken for several months, while its pulse therapy for candidiasis is not approved in Japan. Itraconazole oral solution is commonly used for oral candidiasis, and miconazole gel is also effective.
Topics: Administration, Oral; Administration, Topical; Antifungal Agents; Candida albicans; Candidiasis, Chronic Mucocutaneous; Drug Administration Schedule; Humans; Imidazoles; Ketoconazole; Microscopy; Morpholines; Naphthalenes; Practice Guidelines as Topic; Terbinafine
PubMed: 19942790
DOI: 10.3314/jjmm.50.207 -
Scientific Reports Jul 2022Onycholysis and paronychia has been associated with chemotherapy treatment for women with breast cancer. Our primary aim was to investigate the effectiveness of... (Randomized Controlled Trial)
Randomized Controlled Trial
Onycholysis and paronychia has been associated with chemotherapy treatment for women with breast cancer. Our primary aim was to investigate the effectiveness of different topical interventions to ameliorate nail toxicity. Secondary aims were to explore the full range and severity of possible nail changes associated with taxane-based chemotherapy and the specific impact this had on quality of life, using two novel measures. This was an exploratory randomised controlled trial of three topical interventions (standard care, nail polish or specialist nail drops) for the prevention or reduction of nail changes induced by taxane-based chemotherapy. Outcomes included nail toxicity assessed at three time points (baseline, 3 weeks and 3 months post completion of chemotherapy) using two novel clinical tools (NToX-G12, NToX-QoL) and the Common Terminology Criteria for Adverse Events (CTCAE v3) and EQ-5D-5L. A total of 105 women were recruited (35 in each arm) and monitored up to three months post completion of chemotherapy. Almost 20% of patients were over the age of 60 years. There were 26 withdrawals, the majority from the nail polish arm. Residual Maximum Likelihood REML analysis indicated a significant arm, time and interaction effect for each intervention (p < 0.001). Less nail toxicity was observed in patients receiving specialist nail drops or standard care arms in comparison to those using nail polish. This study provides evidence to support clinicians' suggestions on nail care recommendations based on the patients' needs and preferences. Future investigations into comparing or combining cryotherapy and topical solutions that can support patient's decisions are warranted.
Topics: Breast Neoplasms; Female; Humans; Middle Aged; Nail Diseases; Onycholysis; Quality of Life; Taxoids
PubMed: 35798751
DOI: 10.1038/s41598-022-13327-6