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Cureus Dec 2022Nail changes elicited by Ibrutinib are relatively infrequent but are reported in the literature. Herein, we report on two cases that developed Ibrutinib-induced nail...
Nail changes elicited by Ibrutinib are relatively infrequent but are reported in the literature. Herein, we report on two cases that developed Ibrutinib-induced nail toxicities. A 63-year-old female, with relapsing mantle cell lymphoma on Ibrutinib 560mg/day for seven months developed paronychia, onychomadesis, Beau's lines, nail fragility, and brittleness over fingernails and toenails. On the other hand, an 80-year-old male with chronic lymphoid leukemia developed a bloody papule with hemorrhagic crust and nail-plate abnormalities. Skin toxicities manifested eight months after initiating Ibrutinib therapy. From a clinical perspective, Ibrutinib-induced chronic paronychia and PG have been established. All other PG triggers have been ruled out. After the cessation of Ibrutinib, the PG improved for both cases. The exact pathogenesis of PG induced by Ibrutinib is not yet understood but it had been compared to retinoid-related changes. Thus, further research and reporting of similar cases should be done to further understand the pathophysiology of such manifestations.
PubMed: 36712781
DOI: 10.7759/cureus.32943 -
Enfermedades Infecciosas Y... May 2023
Topics: Humans; Paronychia; Mpox (monkeypox); Anti-Bacterial Agents; Acute Disease
PubMed: 36710164
DOI: 10.1016/j.eimce.2022.09.011 -
Investigational New Drugs Feb 2023Potential novel strategies for adverse event (AE) management of osimertinib therapy, including therapeutic drug monitoring and the use of biomarkers, have not yet been... (Observational Study)
Observational Study
Population Pharmacokinetics, Pharmacogenomics, and Adverse Events of Osimertinib and its Two Active Metabolites, AZ5104 and AZ7550, in Japanese Patients with Advanced Non-small Cell Lung Cancer: a Prospective Observational Study.
BACKGROUND
Potential novel strategies for adverse event (AE) management of osimertinib therapy, including therapeutic drug monitoring and the use of biomarkers, have not yet been fully investigated. This study aimed to evaluate (1) the relationship between exposure to osimertinib, especially its active metabolites (AZ5104 and AZ7550), and AEs, and (2) the relationship between germline polymorphisms and AEs.
METHODS
We conducted a prospective, longitudinal observational study of 53 patients with advanced non-small cell lung cancer receiving osimertinib therapy from February 2019 to April 2022. A population pharmacokinetic model was developed to estimate the area under the serum concentration-time curve from 0 to 24 h (AUC) of osimertinib and its metabolites. Germline polymorphisms were analyzed using TaqMan® SNP genotyping and CycleavePCR® assays.
RESULTS
There was a significant association between the AUC of AZ7550 and grade ≥ 2 paronychia (p = 0.043) or anorexia (p = 0.011) and between that of osimertinib or AZ5104 and grade ≥ 2 diarrhea (p = 0.026 and p = 0.049, respectively). Furthermore, the AUC of AZ5104 was significantly associated with any grade ≥ 2 AEs (p = 0.046). EGFR rs2293348 and rs4947492 were associated with severe AEs (p = 0.019 and p = 0.050, respectively), and ABCG2 rs2231137 and ABCB1 rs1128503 were associated with grade ≥ 2 AEs (p = 0.008 and p = 0.038, respectively).
CONCLUSION
Higher exposures to osimertinib, AZ5104, and AZ7550 and polymorphisms in EGFR, ABCG2, and ABCB1 were related to higher severity of AEs; therefore, monitoring these may be beneficial for osimertinib AE management.
Topics: Humans; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; East Asian People; ErbB Receptors; Lung Neoplasms; Mutation; Pharmacogenetics; Prospective Studies; Protein Kinase Inhibitors; ATP Binding Cassette Transporter, Subfamily B, Member 2; ATP Binding Cassette Transporter, Subfamily B
PubMed: 36637703
DOI: 10.1007/s10637-023-01328-9 -
International Journal of Dermatology Apr 2023Chronic paronychia is an inflammatory process of the nail folds lasting more than 6 weeks. Clinically, there is hypertrophy and retraction of the folds and absence of...
BACKGROUND
Chronic paronychia is an inflammatory process of the nail folds lasting more than 6 weeks. Clinically, there is hypertrophy and retraction of the folds and absence of the cuticle. Treatment involves clinical measures and, when there is no response or the hypertrophy of the folds is very pronounced, surgical treatment is indicated. Post-surgical histopathology is little studied in the literature. In this sense, we believe that the histopathological study is important not only for the individualized understanding of the patient's chronic disease, avoiding relapses, but also for the understanding of its pathophysiology and treatment possibilities.
OBJECTIVE
To describe the histopathological changes found in biopsies of the proximal nail fold of patients with chronic paronychia undergoing surgical treatment.
MATERIALS AND METHODS
A histopathological study of 16 nail folds from 6 patients after surgery was performed at 2 study centers.
RESULTS
The most prevalent epidermal findings were orthokeratosis, hypergranulosis, acanthosis and spongiosis and the dermal findings were fibrosis and mononuclear inflammatory infiltrate.
CONCLUSION
The histopathological study allowed us to conclude that chronic paronychia is primarily an inflammatory process, but it is not possible to conclude whether microorganisms such as Candida and bacterial cocci are part of the etiology or just secondary and opportunistic agents.
Topics: Humans; Paronychia; Nails; Neoplasms; Fibrosis; Chronic Disease; Keratosis; Hypertrophy
PubMed: 36631425
DOI: 10.1111/ijd.16564 -
BMC Medicine Jan 2023HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS...
BACKGROUND
HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS mutations.
METHODS
This was a multicenter phase 1 study. HL-085 was administered twice daily in a standard 3 + 3 dose-escalation design (10 dose cohorts; 0.5-18 mg twice daily), followed by dose expansion at the recommended phase II dose (RP2D). The primary endpoints included tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and RP2D.
RESULTS
Between September 13, 2017, and January 18, 2021, 42 patients were enrolled (dose escalation phase: n = 30; dose expansion phase: n = 12). No DLT was reported during dose escalation and MTD was not reached with HL-085 doses up to 18 mg twice daily. The RP2D was 12 mg twice daily. The most common all-grade drug-related adverse events (AEs) across all dose levels were rash (61.9%), increased creatine phosphokinase (CK, 59.5%), face edema (50.0%), increased aspartate aminotransferase (47.6%), peripheral edema (40.5%), diarrhea (33.3%), alanine aminotransferase (33.3%), and paronychia (19.0%), most of which were grade 1 and 2. Most frequency of grade ≥ 3 AEs were CK (14.2%), asthenia (7.1%), peripheral edema (4.8%), and acneiform dermatitis (4.8%). In the cohort of 12 mg twice daily dose (15 patients), confirmed objective response rate was 26.7%; disease control rate was 86.7%; median duration of response was 2.9 months; median progression-free survival was 3.6 months.
CONCLUSIONS
The HL-085 showed acceptable tolerability and substantial clinical activity in patients with advanced melanoma harboring NRAS mutations.
TRIAL REGISTRATION
Trial registration ClinicalTrials.gov number: NCT03973151.
Topics: Humans; Antineoplastic Agents; GTP Phosphohydrolases; Melanoma; Membrane Proteins; Mitogen-Activated Protein Kinase Kinases; Mutation; Progression-Free Survival; Protein Kinase Inhibitors
PubMed: 36600247
DOI: 10.1186/s12916-022-02669-7 -
Journal of the West African College of... 2022Glomus tumours are benign neoplasms arising from the glomus body, a network of specialized neuromyoarterial structures containing arteriovenous anastomosis and...
INTRODUCTION
Glomus tumours are benign neoplasms arising from the glomus body, a network of specialized neuromyoarterial structures containing arteriovenous anastomosis and regulating temperature. It is often misdiagnosed as paronychia, arthritis, traumatic sequelae, and many other conditions including psychiatric misdiagnosis. A typical triad of paroxysmal pain, point tenderness, and cold intolerance characterize it. Surgical excision is the treatment of choice, either by transungual or lateral approaches.
MATERIALS AND METHODS
We carried out a retrospective study of cases operated in our department in the last 4 years. Patients are evaluated based on either clinical parameters (Love test, Hildreth test, and cold insensitivity) or radiological parameters (X-ray and magnetic resonance imaging). Parameters such as age, gender, tumour side, presenting complaints, duration of symptoms, diagnostic modality, follow-up duration, recurrence, and postoperative nail deformity were analysed. Visual analogue scale (VAS) score was the primary statistical parameter, and the change in VAS score following surgery was analysed with paired test.
RESULT
Mean preoperative VAS was 7.75 ± 0.5; in a total of four patients, and following surgery, VAS was reduced to a mean of 1 ± 1.5. Paired test on the change of VAS score following surgery showed a significant difference in the VAS score ( = 0.002838). The average age was 39.25. The male-to-female ratio was 1:3, and the mean follow-up was 16 months (range 2-48 months). The mean duration of symptoms was 5.75 years (range 2-10 years). Two cases were in the right-hand side, and two cases were on the left-hand side; the thumb was most commonly involved with 50% ( = 2) incidence.
CONCLUSION
Glomus tumours are often misdiagnosed and are intervened with different treatment options before being surgically intervened. With complete surgical excision, recurrence is nil but postoperative nail growth requires nearly 10 months.
LEVEL OF EVIDENCE
Level IV.
PubMed: 36590779
DOI: 10.4103/jwas.jwas_171_22 -
Annales de Dermatologie Et de... Jun 2023
Topics: Humans; Retrospective Studies; Nails; Paronychia; Nails, Ingrown
PubMed: 36577590
DOI: 10.1016/j.annder.2022.11.002 -
Journal of Cutaneous and Aesthetic... 2022Retronychia is an uncommon type of ingrown nail characterized by ingrowing of the proximal nail plate into the proximal nail fold (PNF), inciting cycles of inflammation....
Retronychia is an uncommon type of ingrown nail characterized by ingrowing of the proximal nail plate into the proximal nail fold (PNF), inciting cycles of inflammation. The condition can be symptomatic due to swelling and inflammation of the PNF, but most often it is noticed because of a proximal thickening of the nail plate and the failure of nail to grow distally. It usually affects the great toenails of young females, commonly due to recurrent trauma and footwear-related issues. This condition is difficult to recognize in the initial stages and often requires surgical management when the nail plate becomes significantly impacted. We present a case of retronychia in a 24-year-old lady, who was treated surgically. The report serves to highlight the diagnostic and therapeutic approach in such cases.
PubMed: 36561419
DOI: 10.4103/JCAS.JCAS_248_20 -
Thoracic Cancer Feb 2023Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard treatments for advanced non-small cell lung cancer (NSCLC) patients harboring the...
BACKGROUND
Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard treatments for advanced non-small cell lung cancer (NSCLC) patients harboring the EGFR mutation. Patients experiencing intolerable adverse events (AEs) would discontinue EGFR-TKIs. This study aimed to evaluate the impact of intolerable AEs and subsequent treatment on the survival of patients who discontinued EGFR-TKIs.
PATIENTS
The data of advanced NSCLC patients treated with EGFR-TKIs as frontline treatment at Chang Gung Memorial Hospitals from June 2014 to March 2018 were retrospectively reviewed.
RESULTS
A total of 2190 patients were enrolled and treated with frontline EGFR-TKIs. In August 2021, 114 (5.2%) patients experienced intolerable AEs requiring discontinuation of EGFR-TKIs. The time median of EGFR-TKIs discontinuation was 2.56 months. Age >65 years, females, body weight, and body surface area were associated with the occurrence of intolerable AEs for patients treated with afatinib. Patients experiencing skin/paronychia/mucositis and abnormal liver function test had favorable survivals results. Patients who received subsequent EGFR-TKIs treatment, experienced better progression-free survival (PFS), total PFS (from frontline line EGFR-TKIs), and overall survival (OS) compared to patients receiving chemotherapy or no treatment. Patients undergoing subsequent EGFR-TKIs had better total PFS (median, 14.9 vs. 11.3 months, p = 0.013) and OS (median, 31.3 vs. 20.1 months, p = 0.001) than patients who did not discontinue because of AEs. Favorable OS was validated by propensity score matching.
CONCLUSION
Patients experiencing intolerable AEs during EGFR-TKI treatment should consider switching to an alternative EGFR-TKI, which increase the survival results as compared to those patients who did not experience intolerable AEs.
Topics: Female; Humans; Aged; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Retrospective Studies; Protein Kinase Inhibitors; Disease-Free Survival; ErbB Receptors; Mutation
PubMed: 36525509
DOI: 10.1111/1759-7714.14674 -
BMC Cancer Nov 2022The optimal duration of anti-PD-1 for cancer therapy has not been tested, especially when using combination therapy. Epidermal growth factor receptor (EGFR) pathway...
OBJECTIVES
The optimal duration of anti-PD-1 for cancer therapy has not been tested, especially when using combination therapy. Epidermal growth factor receptor (EGFR) pathway blocker was the top compound that enhanced T-cell killing of tumor cells in a high-throughput immune-oncology screen, possibly by stimulate the antigen presentation machinery and other mechanisms. We explored the effect of combination of EGFR inhibition with a short course of anti-PD-1 therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).
METHOD
We analyzed the effect of a short course of anti-PD-1 with continuous afatinib on the survival of a real-world cohort of R/M HNSCC patients. Patient characteristics, treatments, efficacies, and toxicities were reviewed and recorded for analysis.
RESULTS
From November 2016 to May 2018, 51 consecutive patients received pembrolizumab and afatinib. The cutoff date was June 30, 2022. The most common toxicities (all grades) were diarrhea (62.7%), skin rash (43.1%), mucositis (31.4%), and paronychia (23.5%). The objective response rate was 54.9% (95% confidence interval [CI] 40.3-68.9%). Median progression-free survival was 5.9 months (95% CI: 4.4-7.6 months), and the median overall survival was 10.5 months (95% CI: 6.8-16.5 months). The 12-month, 24-month, 36-month, and 48-month survival rate was 47.0%, 22.5%, 17.7%, and 12.6% respectively.
CONCLUSIONS
This retrospective study showed that short course pembrolizumab with afatinib therapy has acceptable efficacy in R/M HNSCC patients. The durable response and long-term survival rates were similar to prospective clinical trials. Short course anti-PD-1 therapy, especially in combination with EGFR blocker, is worth for further prospective study.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Afatinib; Retrospective Studies; Data Analysis; Prospective Studies; Head and Neck Neoplasms; Carcinoma; ErbB Receptors
PubMed: 36443704
DOI: 10.1186/s12885-022-10343-7