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Clinical Drug Investigation Sep 2019The use of targeted therapies, when added to conventional chemotherapy, has significantly improved clinical outcomes and survival of cancer patients. While targeted... (Review)
Review
The use of targeted therapies, when added to conventional chemotherapy, has significantly improved clinical outcomes and survival of cancer patients. While targeted therapies do not have the systemic adverse reactions of chemotherapy, they are associated with toxicities that can be severe and impair patient quality of life and adherence to anti-cancer treatment. Panitumumab and cetuximab, two monoclonal antibodies against epidermal growth factor receptor (EGFR), are recommended for the treatment of metastatic colorectal cancer (mCRC). The majority of patients with mCRC who are treated with anti-EGFR therapy develop skin toxicities, including papulopustular rash (the most common), xerosis, painful cracks and fissures on the palms and soles of the feet, paronychia, pruritus, and abnormal hair and eyelash growth; they are also more prone to skin infections. Given the involvement of EGFR in normal epidermis physiology, development and function, skin toxicities caused by anti-EGFR therapy are not unexpected. In recent years, recommendations have been formulated for the prevention and treatment of anti-EGFR therapy-related skin toxicities. Indeed, proper and timely management of these toxicities is important for ensuring uninterrupted anti-cancer treatment and optimal outcomes. Here, we review the current knowledge of anti-EGFR therapy-related skin toxicities and the latest recommendations for their management. We also present a treatment approach for papulopustular rash based on the combination of fusidic acid plus betamethasone in a lipid-enriched topical formulation. The effectiveness of this approach is documented by the presentation of five cases successfully treated in clinical practice for anti-EGFR therapy-related rash.
Topics: Antineoplastic Agents, Immunological; Cetuximab; Colorectal Neoplasms; ErbB Receptors; Exanthema; Humans; Neoplasm Metastasis; Panitumumab; Patient Compliance; Practice Guidelines as Topic; Quality of Life
PubMed: 31264159
DOI: 10.1007/s40261-019-00811-7 -
International Journal of Dermatology Feb 2021High rates of posttreatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion resulting from epidermal...
BACKGROUND
High rates of posttreatment discomfort, infection, recurrence, and increased time to return to work have been noted after nail plate avulsion resulting from epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)-induced paronychia, which may even interrupt the course of treatment for EGFR-TKI therapy. Thus, we conducted this study to determine how effectively a topical β-blocker, betaxolol, prevents EGFR-TKI-induced paronychia.
METHODS
This case-control cohort study included a total of 131 non-small-cell lung cancer patients. The prevention group comprised 40 patients treated with topical betaxolol 0.25% solution to prevent paronychia while they received EGFR-TKI therapy. The control group comprised 91 patients who did not preventively use topical betaxolol 0.25% solution while receiving EGFR-TKI therapy. The patients' age, gender, antineoplastic regimen, duration of antineoplastic treatment before the appearance of lesions, number of involved digits (fingernails or toenails) with lesions, grading of paronychia, and pain score were recorded.
RESULTS
In terms of the cumulative incidence of paronychia, significant differences (P < 0.01) were noted at both the 2nd and 3rd months after starting EGFR-TKIs. Furthermore, the average visual analogue scale scores were 3.125 and 6.29 in the prevention group and control group, respectively (P < 0.01). The average grades of paronychia were 1.5 and 2.12 in the prevention group and control group, respectively (P < 0.01). The average numbers of involved digits were 2.25 (range: 1-5 digits) in the prevention group and 3.03 (range: 1-7) in the control group (P = 0.07).
CONCLUSIONS
Preventively using topical betaxolol can significantly decrease the incidence, VAS score, and grading of EGFR-TKI-induced paronychia.
Topics: Antineoplastic Agents; Betaxolol; Carcinoma, Non-Small-Cell Lung; Case-Control Studies; Cohort Studies; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Neoplasm Recurrence, Local; Paronychia; Protein Kinase Inhibitors; Retrospective Studies
PubMed: 32975313
DOI: 10.1111/ijd.15099 -
Journal of the European Academy of... Mar 2024Nondermatophyte moulds (NDMs) are widely distributed and can be detected in association with mycotic nails; however, sometimes it can be challenging to establish the... (Review)
Review
Nondermatophyte moulds (NDMs) are widely distributed and can be detected in association with mycotic nails; however, sometimes it can be challenging to establish the role of NDMs in the pathogenesis of onychomycosis (i.e. causative vs. contaminant). In studies where the ongoing invasive presence of NDMs is confirmed through repeat cultures, the global prevalence of NDMs in onychomycosis patients is estimated at 6.9% with the 3 most common genus being: Aspergillus, Scopulariopsis and Fusarium. NDM onychomycosis can, in many cases, appear clinically indistinguishable from dermatophyte onychomycosis. Clinical features suggestive of NDMs include proximal subungual onychomycosis with paronychia associated with Aspergillus spp., Fusarium spp. and Scopulariopsis brevicaulis, as well as superficial white onychomycosis in a deep and diffused pattern associated with Aspergillus and Fusarium. Longitudinal streaks seen in patients with distal and lateral onychomycosis may serve as an additional indicator. For diagnosis, light microscopic examination should demonstrate fungal filaments consistent with an NDM with at least two independent isolations in the absence of a dermatophyte; the advent of molecular testing combined with histological assessment may serve as an alternative with improved sensitivity and turnover time. In most instances, antifungal susceptibility testing has limited value. Information on effective treatments for NDM onychomycosis is relatively scarce, unlike the situation in the study of dermatophyte onychomycosis. Terbinafine and itraconazole therapy (continuous and pulsed) appear effective to varying extents for treating onychomycosis caused by Aspergillus, Fusarium or Scopulariopsis. There is scant literature on oral treatments for Neoscytalidium.
Topics: Humans; Onychomycosis; Terbinafine; Itraconazole; Treatment Outcome; Paronychia
PubMed: 38010049
DOI: 10.1111/jdv.19644 -
Aerospace Medicine and Human Performance Apr 2020
Topics: Adult; Aerospace Medicine; Animals; Anti-Bacterial Agents; Axilla; Humans; Lymphadenopathy; Male; Military Personnel; Organizational Policy; Paronychia; Pilots; Rabbits; Range of Motion, Articular; Return to Work; Shoulder Pain; Tularemia
PubMed: 32493564
DOI: 10.3357/AMHP.5574.2020 -
Supportive Care in Cancer : Official... Aug 2023Anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies are effective in treating RAS wild-type metastatic colorectal cancer (mCRC). However, their...
PURPOSE
Anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies are effective in treating RAS wild-type metastatic colorectal cancer (mCRC). However, their administration induces skin toxicity, markedly reducing patients' quality of life. This study is aimed at identifying the risk factors associated with anti-EGFR monoclonal antibody-induced skin toxicities.
METHODS
Patients with mCRC (n = 116) who received anti-EGFR monoclonal antibody treatment were retrospectively evaluated. Primary endpoint was evaluation of the risk factors for grade ≥ 2 overall skin toxicities during all the treatment periods. Furthermore, factors associated with each grade ≥ 2 skin symptoms were assessed.
RESULTS
Incidence of total grade ≥ 2 skin toxicity symptoms was 61.2%, and those of grade ≥ 2 rash, dry skin, fissures, and paronychia were 34.5%, 25.9%, 20.7%, and 25.0%, respectively. Multivariate logistic regression analyses revealed that liver metastasis was an independent risk factor for overall grade ≥ 2 skin toxicities (adjusted odds ratio [OR], 2.88; 95% confidence interval [CI], 1.22-6.78; P = 0.02) and prophylactic administration of antibiotics as a preventive factor (OR 0.10; 95%CI 0.01-0.91; P = 0.04). For grade ≥ 2 rash, prophylactic use of systemic antibiotics and topical steroid ointment was a preventive factor (OR 0.37; 95%CI 0.16-0.89; P = 0.03). Moreover, liver metastasis (OR 8.37; 95%CI 1.98-35.47; P = 0.004) and prophylactic administration of antibiotics (OR 0.15; 95%CI 0.03-0.76; P = 0.02) were significantly associated with grade ≥ 2 paronychia.
CONCLUSION
Liver metastasis was suggested to be a risk factor for the incidence of overall grade ≥ 2 skin toxicities; moreover, preemptive systemic antibiotic administration drastically decreased this risk during all periods of anti-EGFR treatment for mCRC.
Topics: Humans; Panitumumab; Cetuximab; Paronychia; Quality of Life; Retrospective Studies; Colorectal Neoplasms; ErbB Receptors; Antibodies, Monoclonal; Antineoplastic Agents; Exanthema; Colonic Neoplasms; Rectal Neoplasms; Anti-Bacterial Agents; Risk Factors
PubMed: 37528282
DOI: 10.1007/s00520-023-07973-3 -
Skin Appendage Disorders Nov 2019Cutaneous manifestations of tuberculosis (TB) are rare, particularly from an exogenous source. Involvement of the nail apparatus is extremely rare and has only...
Cutaneous manifestations of tuberculosis (TB) are rare, particularly from an exogenous source. Involvement of the nail apparatus is extremely rare and has only previously been reported as a secondary involvement. We report the case of a 76-year-old female patient referred to our department with onychodystrophy with purulent drainage of the first left finger, which had developed during the preceding year. She had no previous traumatic history and had received treatment with multiple cycles of oral antibiotics and antimycotics, with no clinical improvement. Physical examination showed paronychia and onychodystrophy of the entire nail plate. Biopsy evaluation revealed epithelioid granulomas with central foci of necrosis, and laboratory cultures were positive for complex. Chest computed tomography excluded primary pulmonary TB. X-ray of the left hand revealed the presence of dactylitis on the distal phalanx. Based on these findings, the patient was treated with rifampicin, isoniazid, pyrazinamide, and ethambutol for 2 months and with rifampicin and isoniazid for 7 months, resulting in complete resolution of the lesions. Cutaneous TB is a diagnostic challenge, particularly in rare cases such as involvement of the nail apparatus. It should be considered as a diagnostic hypothesis in cases of painless paronychia with refractory purulent drainage and associated onychodystrophy.
PubMed: 31799269
DOI: 10.1159/000501698 -
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 -
Journal of Neurosurgical Sciences Dec 2022Selumetinib is a MEK inhibitor, which is effective with an acceptable safety profile in reducing the volume of symptomatic inoperable plexiform neurofibromas in some...
INTRODUCTION
Selumetinib is a MEK inhibitor, which is effective with an acceptable safety profile in reducing the volume of symptomatic inoperable plexiform neurofibromas in some clinical trials and also has been recently approved by FDA for use in children aged 2 years or older. However, no systematic review has yet been performed to provide a collective estimate of the results of all these trials.
EVIDENCE ACQUISITION
Articles describing the use of selumetinib in patients with neurofibromatosis type-1 (NF1) with inoperable plexiform neurofibromas were searched from different electronic databases. The objectives were to provide a pooled estimate of efficacy evaluated by direct measurement and also by various functional measures, as well as the proportion of patients with adverse events. For determining pooled estimates, we included only studies with a minimum sample size of 15 with a prospective study design.
EVIDENCE SYNTHESIS
A total of eight articles with 137 patients were found and 134 patients in six uncontrolled trials were included in the quantitative review. Out of these 26 were adults (69% male; 33.2±18.4 years, range 18-60 years) and 108 were in the pediatric age group (74% boys, 10.9±2.3 years, range-2-18 years,). Total 77.86% (95% CI: 55.91-99.81%) patients had a partial response, 71.24% (95% CI: 53.62-89.93%) had a confirmed partial response, and 56.25% (95% CI: 37.53-72.49%) had a durable partial response. The average time to initial response was 7.3±2.9 cycles (range, 4 to 20), and the median time to best response was 15.4±5.8 cycles (range, 4 to 36). The average change in neurofibroma volume at best response was -28.15% (95% CI: -17.95%, -38.34%, range, -55.1% to 2.2%). Progression-free survival was observed in 93.12% of patients at the time of data cut-off. Overall, 73.26% (95% CI: 54.07%, 92.45%) patients had improvement in at least one of the functional or patient-reported outcome assessments. The most common adverse effects were grade 1 and 2 gastrointestinal symptoms (65%), an asymptomatic increase in the creatine phosphokinase level (31%), paronychia (6%), and acneiform rash (17%). A total of 17% patients required dose reduction due to these toxic effects and 10.5% (95% CI: 4.0%, 17.0%) of patients discontinued due to toxic effects.
CONCLUSIONS
Selumetinib can produce sustained shrinkage in the majority of patients with NF1 and symptomatic plexiform neurofibroma to provide clinically meaningful benefit in functional ability, with more robust evidence in children. The acceptable safety profile and absence of cumulative toxic effects permit long-term treatment with selumetinib.
Topics: Adult; Humans; Male; Child; Female; Neurofibroma, Plexiform; Prospective Studies; Benzimidazoles; Neurofibromatosis 1
PubMed: 35301838
DOI: 10.23736/S0390-5616.21.05528-4 -
Targeted Oncology Jul 2023In RELAY, a randomized, double-blind, phase III trial investigating the efficacy and safety of ramucirumab+erlotinib (RAM+ERL) or ERL+placebo (PBO) in patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Tolerability of Ramucirumab Plus Erlotinib in Taiwanese Patients with Untreated, Epidermal Growth Factor Receptor-Mutated, Stage IV Non-small Cell Lung Cancer in the RELAY Study.
BACKGROUND
In RELAY, a randomized, double-blind, phase III trial investigating the efficacy and safety of ramucirumab+erlotinib (RAM+ERL) or ERL+placebo (PBO) in patients with untreated, stage IV, epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), RAM+ERL demonstrated superior progression-free survival (PFS) versus PBO+ERL, with no new safety signals.
OBJECTIVE
The aim of this paper was to report efficacy and tolerability findings for the Taiwanese participants of RELAY.
PATIENTS AND METHODS
Patients were randomized 1:1 to RAM+ERL or ERL+PBO. Primary endpoint was investigator-assessed PFS. Secondary endpoints included objective response rate (ORR), duration of response (DoR) and tolerability. Data for the current analysis are reported descriptively.
RESULTS
In RELAY, 56 Taiwanese patients were enrolled; 26 received RAM+ERL, 30 received ERL+PBO. The demographic profile of the Taiwanese subgroup was consistent with that of the overall RELAY population. Median PFS for RAM+ERL/ERL+PBO, respectively, was 22.05 months/13.40 months (unstratified hazard ratio 0.4; 95% confidence interval 0.2-0.9); ORR was 92%/60%; median DoR was 18.2 months/12.7 months. All patients experienced one or more treatment-emergent adverse events (TEAEs); those most commonly reported were diarrhea and dermatitis acneiform (58% each) for RAM+ERL and diarrhea (70%) and paronychia (63%) for PBO+ERL. Grade ≥ 3 TEAEs were experienced by 62%/30% of RAM+ERL/PBO+ERL patients, respectively, and included dermatitis acneiform (19%/7%), hypertension (12%/7%), and pneumonia (12%/0%).
CONCLUSIONS
PFS for the Taiwanese participants of RELAY receiving RAM+ERL versus ERL+PBO was consistent with that in the overall RELAY population. These results, together with no new safety signals and a manageable safety profile, may support first-line use of RAM+ERL in Taiwanese patients with untreated EGFR-mutant stage IV NSCLC.
TRIAL REGISTRATION
www.
CLINICALTRIALS
gov , NCT02411448.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride; Lung Neoplasms; Antineoplastic Combined Chemotherapy Protocols; ErbB Receptors; Diarrhea; Dermatitis; Mutation; Ramucirumab
PubMed: 37329423
DOI: 10.1007/s11523-023-00975-5 -
European Journal of Trauma and... Apr 2022No standardized execution or evidence demonstrates the area of the digit giving the most accurate capillary refill time (CRT). This study investigated the reliability...
PURPOSE
No standardized execution or evidence demonstrates the area of the digit giving the most accurate capillary refill time (CRT). This study investigated the reliability and validity of CRT, and the relative merits of areas where the test could be performed.
METHODS
In all, 127 healthy volunteers were assessed for normal CRT at the fingernail, lateral paronychia, and proximal and distal pulps of the index finger. The predictive validity of the CRT for the diagnosis of compromised vascular perfusion was also investigated on 24 subjects, using an inflated tourniquet. Three raters assessed interobserver reliability.
RESULTS
The mean fingernail, lateral paronychia, proximal pulp, and distal pulp CRTs were 1.93, 1.78, 1.70, and 1.57 s, respectively. The tourniquet and non-tourniquet results demonstrated significant mean differences; however, the fingernail showed a subtle difference (1.22 s) compared with the proximal pulp (4.46 s). The CRT interobserver reliability was fair at the fingernail (intraclass correlation coefficient [ICC] = 0.51), but very poor in occluded limbs (ICC = 0.13). At the lateral paronychia and finger pulp, the interobserver reliability was reasonable (ICC = 0.75-0.81 [non-tourniquet] vs 0.62-0.68 [tourniquet]). In a receiver-operating characteristic curve analysis, the proximal pulp demonstrated better discrimination (area under the curve = 0.93, 95% CI 0.89-0.97, p < 0.0001); the best cutoff point was calculated to be 3 s at the proximal pulp.
CONCLUSIONS
CRT use at appropriate areas is reliable. The most dependable site is the finger pulp, and the proposed cutoff is 3 s.
Topics: Capillaries; Fingers; Humans; Paronychia; Perfusion; Reproducibility of Results
PubMed: 33475776
DOI: 10.1007/s00068-020-01594-9