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Revista Medica de Chile May 2021Taxanes are a class of chemotherapeutic agents with common associated dermatologic adverse events, such as skin hyperpigmentation, hand-foot skin syndrome, paronychia...
Taxanes are a class of chemotherapeutic agents with common associated dermatologic adverse events, such as skin hyperpigmentation, hand-foot skin syndrome, paronychia and onycholysis. Taxane-induced scleroderma is rare. Few cases with skin findings resembling systemic sclerosis, have been reported after the administration of these agents. We report two cases with stage IV breast cancer, aged 66 and 71 years, who developed sclerodermic skin lesions in their extremities after starting treatment with placlitaxel and nabplaclitaxel respectively.
Topics: Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Female; Humans; Scleroderma, Systemic; Taxoids
PubMed: 34751336
DOI: 10.4067/s0034-98872021000500807 -
American Family Physician Apr 2014
Topics: Aged; Chronic Disease; Diagnosis, Differential; Edema; Humans; Male; Paronychia; Thumb
PubMed: 24784125
DOI: No ID Found -
JTO Clinical and Research Reports Dec 2023Osimertinib may be effective in treating central nervous system (CNS) metastasis, but its efficacy in treating radiation therapy (RT)-naive metastasis is unclear. The...
A Phase 2 Single-Arm Study of Osimertinib for Radiotherapy-Naive Central Nervous System Metastasis NSCLC: Results for the First-Line Cohort of the OCEAN Study (LOGIK 1603/WJOG 9116L).
INTRODUCTION
Osimertinib may be effective in treating central nervous system (CNS) metastasis, but its efficacy in treating radiation therapy (RT)-naive metastasis is unclear. The OCEAN study assessed the efficacy of osimertinib against RT-naive CNS metastasis in patients previously treated (T790M cohort) and untreated patients (first-line cohort) with mutation. Here, we report the results of the first-line cohort.
METHODS
Previously untreated patients with RT-naive CNS metastasis and mutation-positive NSCLC were treated with osimertinib. The brain metastasis response rate (BMRR), progression-free survival (PFS), and overall survival in the first-line cohort were secondary end points.
RESULTS
A total of 26 patients were enrolled in the study between September 2019 and July 2020. The median age was 72.0 years with 80.8% female. There were 20 patients who had multiple CNS metastases. BMRR assessed by PAREXEL criteria was 76.9% (90% confidence interval [CI]: 63.3%-90.5%), BMRR assessed by Response Evaluation Criteria in Solid Tumors was 76.9% (95% CI: 54.0%-99.8%), and median PFS of CNS metastasis was 22.0 months (95% CI: 9.7 mo-not reached). The overall response rate was 64.0% (95% CI: 45.2%-82.8%), median PFS was 11.5 months (95% CI: 6.9 mo-not reached), and median survival time was 23.7 months (95% CI: 16.5 mo-not reached). Paronychia and increased creatinine level were the most frequent nonhematological toxicities observed in 13 patients (50%). Grade three and higher adverse events were less than 10%, and there were no treatment-related deaths. Pneumonitis was observed in five patients (19.2%).
CONCLUSIONS
These results suggest that osimertinib is effective in untreated patients with RT-naive asymptomatic CNS metastasis in a clinical practice first-line setting.
TRIAL REGISTRATION
UMIN identifier: UMIN000024218. jRCT identifier: jRCTs071180017.
PubMed: 38046380
DOI: 10.1016/j.jtocrr.2023.100587 -
Skin Appendage Disorders Jan 2017Vandetanib therapy is a novel once-daily oral multitargeted tyrosine kinase inhibitor, which is currently used in advanced or metastatic medullary thyroid cancer. Skin...
Vandetanib therapy is a novel once-daily oral multitargeted tyrosine kinase inhibitor, which is currently used in advanced or metastatic medullary thyroid cancer. Skin toxicities are among the most prevalent adverse events reported with this targeted therapy (e.g. acne-like rash, hand-foot skin reaction, hair changes, and paronychia). In addition, photosensitivity reactions may affect more than one third of treated patients. We report here 2 patients developing photosensitivity reactions with vandetanib therapy, including photoonycholysis. Our patients presented a wide range of phototoxic reactions with exaggerated sunburn reactions solely located to photoexposed areas or hyperpigmentation with visible blue dots. More importantly, both patients concomitantly developed nail changes consistent with type 1 photoonycholysis, which had never been reported so far neither with vandetanib therapy nor with other anticancer-targeted therapies. In addition, histopathologic findings and reflectance confocal microscopy imaging performed in one patient suffering from photodistributed skin hyperpigmentation both strengthen the likelihood of a postinflammatory mechanism. Clinicians should be aware of these underestimated but very characteristic photoinduced adverse events, which can lead to treatment interruption and require very strict photoprotective measures in treated patients.
PubMed: 28232923
DOI: 10.1159/000452425 -
Journal of the Advanced Practitioner in... 2016New advances in the treatment of non-small cell lung cancer (NSCLC) have afforded patients longer progression-free survival times, but these therapies are also... (Review)
Review
New advances in the treatment of non-small cell lung cancer (NSCLC) have afforded patients longer progression-free survival times, but these therapies are also associated with specific side effects that may not be seen with chemotherapy or radiotherapy. One class of agents includes the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), which have been shown to be efficacious in patients whose tumors harbor -activating mutations. Certain adverse effects, particularly rash and diarrhea, as well as mucositis/stomatitis, paronychia, ocular disorders, and interstitial lung disease, are seen with this class as a function of their mechanism of action. This review presents the suggested pathogenesis of these toxicities as well as specific management strategies to assist advanced practitioners in helping patients receive the full benefit of treatment with EGFR TKIs.
PubMed: 29670808
DOI: No ID Found -
Journal of Traditional and... Sep 2020Cancer is a major public health problem worldwide, and there has been a sustained rise in its incidence in both developing and developed countries. Although there are... (Review)
Review
Cancer is a major public health problem worldwide, and there has been a sustained rise in its incidence in both developing and developed countries. Although there are currently numerous effective therapeutic options for cancer, they sometimes exhibit resistance and obvious side effects. Traditional Chinese medicine (TCM) currently plays a major role in cancer therapy by downregulating the growth of cancer cells through various pathways and by relieving side effects. Studies in cultured human malignant cell lines have demonstrated that can control cancer cell proliferation and cancer progression by inducing autophagic and apoptotic cell death. Case-control studies have indicated that TCM can relieve the side effects of cancer therapy. This review provides brief insights into the anticancer effects of TCM, the side effects relieved by TCM, and the role of TCM doctors in cancer treatment.
PubMed: 32953557
DOI: 10.1016/j.jtcme.2019.07.001 -
Medical Mycology Journal 2016Oral antifungal drugs are used primarily to treat tinea unguium; however, they are also useful for other types of tinea. For example, a combination of topical and oral... (Review)
Review
Oral antifungal drugs are used primarily to treat tinea unguium; however, they are also useful for other types of tinea. For example, a combination of topical and oral antifungal drugs is effective in hyperkeratotic tinea pedis that is unresponsive to topical monotherapy. In cases of tinea facialis adjacent to the eyes, ears, or mouth, or widespread tinea corporis, or tinea cruris involving the complex skin folds of the external genitalia, it is difficult to apply topical drugs to all the lesions; therefore, oral antifungal drugs are necessary. Oral antifungal drugs are also useful not only for tinea but for widespread pityriasis versicolor and Malassezia folliculitis, candidal onychomycosis, and candidal paronychia and onychia. Topical antifungal drugs are in fact unsuitable for some mycoses. In tinea capitis, for example, irritation by topical drugs is likely to enhance inflammation; therefore, oral antifungal drug monotherapy is preferable. In interdigital tinea pedis with erosion or contact dermatitis, topical drugs are difficult to use because they tend to cause irritant dermatitis, resulting in exacerbation of the condition. In such cases, treatment should begin with a combination of topical corticosteroid therapy and oral antifungal drugs active against dermatophytes. Topical antifungal drugs are used after the complications resolve. A combination of topical and oral antifungal drugs can shorten the treatment period, thus improving patient adherence to topical treatment. Oral antifungal drugs are useful because of their wide range of applications in the treatment of dermatomycosis.
Topics: Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Antifungal Agents; Dermatomycoses; Drug Therapy, Combination; Humans; Patient Compliance; Severity of Illness Index
PubMed: 27251319
DOI: 10.3314/mmj.57.J71 -
Journal of Oncology 2021The purpose of this study was to explore the efficacy and safety of afatinib in advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor...
INTRODUCTION
The purpose of this study was to explore the efficacy and safety of afatinib in advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations based on real-world evidence.
MATERIALS AND METHODS
Eligible real-world studies were identified from PubMed, Cochrane Library, and Embase. Cochrane guidelines were used to assess the quality of included studies. Cochran's test and I statistics were used for the heterogeneity analysis.
RESULTS
Twenty-five studies were included in this meta-analysis; nine studies were included in the qualitative descriptive analysis. The summarized disease control rate (DCR) was 87.6% (81.5%, 92.7%), and the overall response rate (ORR) was 58.9% (48.8%, 68.7%). The pooled median progression-free survival (PFS) was 12.4 (10.3, 14.5) months, mean time to failure (TTF) was 15.4 (13.6, 17.2) months, and median overall survival (OS) was 31.6 (26.7, 36.5) months. The total incidences of adverse events (AEs) for skin rashes, diarrhea, paronychia, and mucositis were 71.4% (64.4%, 77.9%), 70.4% (60.1%, 79.8%), 52.1% (41.9, 62.3%), and 36.5% (29.5%, 43.8%), respectively. The incidences of severe adverse events (SAEs, Grade ≥3) for diarrhea, skin rashes, paronychia, and mucositis were 9.7% (6.8%, 13.1%), 5.8% (4.5%, 7.2%), 3.8% (2.0%, 6.2%), and 2.1% (1.0%, 3.6%), respectively. Differences in PFS and OS between the afatinib non-full-dose (<40 mg) and full-dose (>40 mg) groups were not significant ( > 0.05). However, the ORR in the full-dose group was 78.5% (66.7%, 88.4%), which was significantly higher than that in the non-full-dose group (67.8% [56.8%, 77.9%]).
CONCLUSION
The efficacy and safety of afatinib has been confirmed by real-world evidence in advanced NSCLC with EGFR mutation, consistent with randomized controlled trial results. In real-world setting, tolerability-guided dose adjustment might not affect the afatinib efficacy.
PubMed: 34961817
DOI: 10.1155/2021/8736288 -
The Cochrane Database of Systematic... Jan 2020Onychomycosis refers to fungal infections of the nail apparatus that may cause pain, discomfort, and disfigurement. This is an update of a Cochrane Review published in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Onychomycosis refers to fungal infections of the nail apparatus that may cause pain, discomfort, and disfigurement. This is an update of a Cochrane Review published in 2007; a substantial amount of new research warrants a review exclusively on toenails.
OBJECTIVES
To assess the clinical and mycological effects of topical drugs and device-based therapies for toenail onychomycosis.
SEARCH METHODS
We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials registers, and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
Randomised controlled trials of topical and device-based therapies for onychomycosis in participants with toenail onychomycosis, confirmed by positive cultures, direct microscopy, or histological nail examination. Eligible comparators were placebo, vehicle, no treatment, or an active topical or device-based treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcomes were complete cure rate (normal-looking nail plus fungus elimination, determined with laboratory methods) and number of participants reporting treatment-related adverse events.
MAIN RESULTS
We included 56 studies (12,501 participants, average age: 27 to 68 years), with mainly mild-to-moderate onychomycosis without matrix involvement (where reported). Participants had more than one toenail affected. Most studies lasted 48 to 52 weeks; 23% reported disease duration (variable). Thirty-five studies specifically examined dermatophyte-caused onychomycosis. Forty-three studies were carried out in outpatient settings. Most studies assessed topical treatments, 9% devices, and 11% both. We rated three studies at low risk of bias across all domains. The most common high-risk domain was performance bias. We present results for key comparisons, where treatment duration was 36 or 48 weeks, and clinical outcomes were measured at 40 to 52 weeks. Based on two studies (460 participants), compared with vehicle, ciclopirox 8% lacquer may be more effective in achieving complete cure (risk ratio (RR) 9.29, 95% confidence interval (CI) 1.72 to 50.14; low-quality evidence) and is probably more effective in achieving mycological cure (RR 3.15, 95% CI 1.93 to 5.12; moderate-quality evidence). Ciclopirox lacquer may lead to increased adverse events, commonly application reactions, rashes, and nail alteration (e.g. colour, shape). However, the 95% CI indicates that ciclopirox lacquer may actually make little or no difference (RR 1.61, 95% CI 0.89 to 2.92; low-quality evidence). Efinaconazole 10% solution is more effective than vehicle in achieving complete cure (RR 3.54, 95% CI 2.24 to 5.60; 3 studies, 1716 participants) and clinical cure (RR 3.07, 95% CI 2.08 to 4.53; 2 studies, 1655 participants) (both high-quality evidence) and is probably more effective in achieving mycological cure (RR 2.31, 95% CI 1.08 to 4.94; 3 studies, 1716 participants; moderate-quality evidence). Risk of adverse events (such as dermatitis and vesicles) was slightly higher with efinaconazole (RR 1.10, 95% CI 1.01 to 1.20; 3 studies, 1701 participants; high-quality evidence). No other key comparison measured clinical cure. Based on two studies, compared with vehicle, tavaborole 5% solution is probably more effective in achieving complete cure (RR 7.40, 95% CI 2.71 to 20.24; 1198 participants), but probably has a higher risk of adverse events (application site reactions were most commonly reported) (RR 3.82, 95% CI 1.65 to 8.85; 1186 participants (both moderate-quality evidence)). Tavaborole improves mycological cure (RR 3.40, 95% CI 2.34 to 4.93; 1198 participants; high-quality evidence). Moderate-quality evidence from two studies (490 participants) indicates that P-3051 (ciclopirox 8% hydrolacquer) is probably more effective than the comparators ciclopirox 8% lacquer or amorolfine 5% in achieving complete cure (RR 2.43, 95% CI 1.32 to 4.48), but there is probably little or no difference between the treatments in achieving mycological cure (RR 1.08, 95% CI 0.85 to 1.37). We found no difference in the risk of adverse events (RR 0.60, 95% CI 0.19 to 1.92; 2 studies, 487 participants; low-quality evidence). The most common events were erythema, rash, and burning. Three studies (112 participants) compared 1064-nm Nd:YAG laser to no treatment or sham treatment. We are uncertain if there is a difference in adverse events (very low-quality evidence) (two studies; 85 participants). There may be little or no difference in mycological cure at 52 weeks (RR 1.04, 95% CI 0.59 to 1.85; 2 studies, 85 participants; low-quality evidence). Complete cure was not measured. One study (293 participants) compared luliconazole 5% solution to vehicle. We are uncertain whether luliconazole leads to higher rates of complete cure (very low-quality evidence). Low-quality evidence indicates there may be little or no difference in adverse events (RR 1.02, 95% CI 0.90 to 1.16) and there may be increased mycological cure with luliconazole; however, the 95% CI indicates that luliconazole may make little or no difference to mycological cure (RR 1.39, 95% CI 0.98 to 1.97). Commonly-reported adverse events were dry skin, paronychia, eczema, and hyperkeratosis, which improved or resolved post-treatment.
AUTHORS' CONCLUSIONS
Assessing complete cure, high-quality evidence supports the effectiveness of efinaconazole, moderate-quality evidence supports P-3051 (ciclopirox 8% hydrolacquer) and tavaborole, and low-quality evidence supports ciclopirox 8% lacquer. We are uncertain whether luliconazole 5% solution leads to complete cure (very low-quality evidence); this outcome was not measured by the 1064-nm Nd:YAG laser comparison. Although evidence supports topical treatments, complete cure rates with topical treatments are relatively low. We are uncertain if 1064-nm Nd:YAG laser increases adverse events compared with no treatment or sham treatment (very low-quality evidence). Low-quality evidence indicates that there is no difference in adverse events between P-3051 (ciclopirox hydrolacquer), luliconazole 5% solution, and their comparators. Ciclopirox 8% lacquer may increase adverse events (low-quality evidence). High- to moderate-quality evidence suggests increased adverse events with efinaconazole 10% solution or tavaborole 5% solution. We downgraded evidence for heterogeneity, lack of blinding, and small sample sizes. There is uncertainty about the effectiveness of device-based treatments, which were under-represented; 80% of studies assessed topical treatments, but we were unable to evaluate all of the currently relevant topical treatments. Future studies of topical and device-based therapies should be blinded, with patient-centred outcomes and an adequate sample size. They should specify the causative organism and directly compare treatments.
Topics: Administration, Topical; Adult; Aged; Antifungal Agents; Female; Humans; Male; Middle Aged; Onychomycosis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31978269
DOI: 10.1002/14651858.CD012093.pub2 -
RSC Advances Jun 2021The chemical characterization of the extract of the aerial parts of afforded two oxetane containing lignans, paronychiarabicine A (1) and B (2), and one new...
The chemical characterization of the extract of the aerial parts of afforded two oxetane containing lignans, paronychiarabicine A (1) and B (2), and one new megastigmane, paronychiarabicastigmane A (3), alongside a known lignan (4), eight known phenolic compounds (5-12), one known elemene sesquiterpene (13) and one steroid glycoside (14). The chemical structures of the isolated compounds were constructed based upon the HRMS, 1D, and 2D-NMR results. The absolute configurations were established NOESY experiments as well as experimental and TDDFT-calculated electronic circular dichroism (ECD). Utilizing molecular docking, the binding scores and modes of compounds 1-3 towards the SARS-CoV-2 main protease (M), papain-like protease (PL), and RNA-dependent RNA polymerase (RdRp) were revealed. Compound 3 exhibited a promising docking score (-9.8 kcal mol) against SARS-CoV-2 M by forming seven hydrogen bonds inside the active site with the key amino acids. The reactome pathway enrichment analysis revealed a correlation between the inhibition of and genes (identified as the main targets of megastigmane treatment) and significant inhibition of SARS-CoV-1 viral replication in infected Vero E6 cells. Our results manifest a novel understanding of genes, proteins and corresponding pathways against SARS-CoV-2 infection and could facilitate the identification and characterization of novel therapeutic targets as treatments of SARS-CoV-2 infection.
PubMed: 35479905
DOI: 10.1039/d1ra02486h