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1.
Acta Derm Venereol ; 104: adv40555, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39192813

RESUMEN

Skin toxicities caused by epidermal growth factor receptor tyrosine kinase inhibitors can affect patient quality of life and lead to treatment adjustments, including dose reduction or discontinuation. This retrospective study aimed to profile skin toxicities and their impact on treatment adjustments. A total of 288 non-small cell lung cancer patients treated with first-, second-, or third-generation epidermal growth factor receptor tyrosine kinase inhibitors were included. Skin toxicities, including papulopustular rash, xerosis, paronychia, and pruritus, were assessed based on medical records, and their severity was evaluated based on the required dermatological intervention. Papulopustular rash was the most common toxicity (74.3%), followed by pruritus (61.1%), xerosis (52.4%), and paronychia (39.6%). Papulopustular rash was more common in males and more severe in younger patients. Papulopustular rash was more prevalent in patients treated with first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors, while paronychia was notably frequent for the second-generation epidermal growth factor receptor tyrosine kinase inhibitors. Second-generation epidermal growth factor receptor tyrosine kinase inhibitors frequently caused multiple skin toxicities. Importantly, skin toxicities led to epidermal growth factor receptor tyrosine kinase inhibitor treatment adjustments in 26.7% of cases, with second-generation epidermal growth factor receptor tyrosine kinase inhibitors demonstrating higher adjustment rates. Papulopustular rash and paronychia were the main causes of treatment adjustments, with even mild paronychia being linked to treatment adjustments. Effective management of skin toxicities is essential for optimizing treatment outcomes in patients receiving epidermal growth factor receptor tyrosine kinase inhibitors.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Erupciones por Medicamentos , Receptores ErbB , Neoplasias Pulmonares , Inhibidores de Proteínas Quinasas , Humanos , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Femenino , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas/efectos adversos , Receptores ErbB/antagonistas & inhibidores , Anciano , Persona de Mediana Edad , Erupciones por Medicamentos/etiología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Antineoplásicos/efectos adversos , Anciano de 80 o más Años , Adulto , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Factores de Riesgo , Paroniquia/inducido químicamente
2.
Dermatology ; 240(4): 565-571, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38772345

RESUMEN

INTRODUCTION: Mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors are in use for several indications for adults and children. Cutaneous toxicities are among the most common adverse effects. We aimed to describe the spectrum of cutaneous adverse events, its frequency, and severity in a cohort of pediatric patients. METHODS: We reviewed all records of patients in our tertiary treatment center treated with MEK inhibitors between January 2016 and January 2023 for all indications. RESULTS: Among 33 patients, 76% reported cutaneous adverse effects. The highest prevalence was in the group of patients treated with trametinib (90%), followed by the group treated with selumetinib (50%) and the group treated with a combination of trametinib and B-Raf proto-oncogene serine/threonine-protein kinase inhibitor (dabrafenib, 34%). Xerosis, dermatitis, paronychia, and hair heterochromia were most frequently reported. Severity was graded 1 or 2 for most adverse events, and 237 visits to the dermatology clinic related to these adverse events were recorded. CONCLUSIONS: Cutaneous adverse events are common in the pediatric population as in adults, but the clinical spectrum is different. Although considered mild, multiple dermatological consultations reflect the distress caused by these events. Dermatologists have a central role in the multidisciplinary care of pediatric patients receiving these agents.


Asunto(s)
Erupciones por Medicamentos , Inhibidores de Proteínas Quinasas , Proto-Oncogenes Mas , Humanos , Estudios Retrospectivos , Masculino , Femenino , Niño , Adolescente , Preescolar , Erupciones por Medicamentos/etiología , Inhibidores de Proteínas Quinasas/efectos adversos , Piridonas/efectos adversos , Pirimidinonas/efectos adversos , Lactante , Índice de Severidad de la Enfermedad , Imidazoles/efectos adversos , Oximas/efectos adversos , Oximas/uso terapéutico , Bencimidazoles/efectos adversos , Paroniquia/inducido químicamente
3.
J Oncol Pharm Pract ; 30(2): 295-303, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37098185

RESUMEN

INTRODUCTION: Despite the common occurrence of cetuximab (Cmab)-induced skin toxicity, management strategies are not well established. The traditional mainstay method consists of topical steroids, which, if used excessively, may give rise to other concerns. Alternatively, adapalene can activate epidermal growth factor receptor pathways to potentially alleviate these toxicities. METHODS: We prospectively studied 31 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) who were eligible to use adapalene gel as a reactive treatment for topical steroid-refractory skin toxicity. For comparison, we retrospectively reviewed 99 patients with R/M SCCHN (historical control cohort) whose skin toxicity was mainly treated with topical steroids. We compared the frequency and severity of Cmab-induced skin toxicity, Cmab therapy status (e.g., dose modification), side effects caused by topical steroids and adapalene gel itself, and other medical interventions. RESULTS: Adapalene gel was used by eight patients (25.8%) in the prospective cohort. Patients in the historical control cohort more frequently required escalation of topical steroid potency (34.3% vs. 12.9%, p = 0.022). Although there was no statistically significant difference in the frequency of grade ≥3 facial skin rash and paronychia between the two cohorts, the prospective cohort showed a significantly shorter time to complete recovery from grade 2/3 paronychia (16 vs. 47 days, p = 0.017). Further, while no skin infections were observed in the prospective cohort, 13 patients in the historical control cohort developed skin infections, especially periungual infection (0% vs. 13.1%, p = 0.024). In addition, no patients in the prospective cohort received a dose reduction of Cmab due to skin toxicities, compared to 20 patients in the historical control cohort (0% vs. 20.2%, p = 0.003). No apparent adapalene gel-related side effects were observed. CONCLUSIONS: Adapalene gel may be an effective management option for topical steroid-refractory Cmab-induced skin toxicities and could improve compliance with Cmab therapy.


Asunto(s)
Neoplasias de Cabeza y Cuello , Paroniquia , Enfermedades de la Piel , Humanos , Cetuximab/efectos adversos , Adapaleno/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Estudios Prospectivos , Estudios Retrospectivos , Paroniquia/inducido químicamente , Paroniquia/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Enfermedades de la Piel/inducido químicamente , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Esteroides , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
4.
Support Care Cancer ; 31(8): 504, 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37528282

RESUMEN

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.


Asunto(s)
Antineoplásicos , Neoplasias del Colon , Neoplasias Colorrectales , Exantema , Paroniquia , Neoplasias del Recto , Humanos , Panitumumab/efectos adversos , Cetuximab/efectos adversos , Paroniquia/inducido químicamente , Calidad de Vida , Estudios Retrospectivos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Receptores ErbB/metabolismo , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Exantema/inducido químicamente , Antibacterianos/uso terapéutico , Factores de Riesgo
5.
Australas J Dermatol ; 64(3): e245-e251, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37224380

RESUMEN

The cutaneous toxicity of MEK inhibitors may limit treatment adherence. The authors present a retrospective study of 41 paediatric patients with NF-1 undergoing therapy with selumetinib and propose a treatment algorithm.


Asunto(s)
Paroniquia , Enfermedades de la Piel , Humanos , Niño , Estudios Retrospectivos , Paroniquia/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Enfermedades de la Piel/inducido químicamente , Quinasas de Proteína Quinasa Activadas por Mitógenos/efectos adversos
6.
Anticancer Res ; 43(4): 1775-1783, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36974789

RESUMEN

BACKGROUND/AIM: Osimertinib is a key drug for treating epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Genetic differences may be associated to adverse events (AEs) induced by osimertinib. This retrospective observational multicenter study evaluated the association of genotypes, including STAT3 -1697C>G, CYP3A5 6986A>G, and ABCG2 421C>A, with the incidence of osimertinib-induced AEs in patients with EGFR mutation-positive NSCLC. PATIENTS AND METHODS: A total of 85 patients treated with osimertinib (Institution A: 33 patients, Institution B: 52 patients) were enrolled in the study. Single nucleotide polymorphisms were determined by real-time PCR, and the incidence of AEs was compared for each genotype. RESULTS: Paronychia incidence was 59% for the CC genotype, 19% for the CG genotype, and 19% for the GG genotype at STAT3 -1697C>G. A genotype-related trend was observed (Cochran-Armitage test, p=0.009). Multivariate analysis showed that the CC genotype at STAT3 -1697C>G and female sex were significant independent factors associated with paronychia [odds ratio (OR)=6.41, 95% confidence interval (CI)=1.94-21.20 and OR=3.40, 95%CI=1.03-11.22, respectively]. The incidence of diarrhea was 53% for the CC genotype, 30% for the AC genotype, and 29% for the AA genotype at ABCG2 421C>A, and a genotype-related trend was observed (p=0.048). However, the CC genotype at ABCG2 421C>A was not a significant independent factor associated with diarrhea in multivariate analysis. No significant associations were detected between other polymorphisms and the incidence of AEs. CONCLUSION: STAT3 -1697C>G may be a novel risk factor for osimertinib-induced paronychia in patients with NSCLC.


Asunto(s)
Compuestos de Anilina , Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Paroniquia , Inhibidores de Proteínas Quinasas , Femenino , Humanos , Compuestos de Anilina/efectos adversos , Compuestos de Anilina/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Citocromo P-450 CYP3A/genética , Diarrea/inducido químicamente , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Paroniquia/inducido químicamente , Polimorfismo de Nucleótido Simple , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , Factor de Transcripción STAT3/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética
7.
Immunopharmacol Immunotoxicol ; 45(1): 1-9, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35950851

RESUMEN

AIM: Cetuximab and panitumumab are common antibodies against epidermal growth factor receptor (EGFR) that can be used in combination with chemotherapy for the treatment of metastatic colorectal cancer (mCRC). Although these two drugs are considered to be very similar, differences in the efficacy and safety of cetuximab and panitumumab are still unclear. We conducted this meta-analysis to explore the effects and adverse reactions of cetuximab and panitumumab in the treatment of mCRC. METHODS: We searched PubMed, the Cochrane Library, Embase, Web of Science, China national knowledge infrastructure (CNKI) and WanFang databases to identify records related to the efficacy and safety of cetuximab and panitumumab in the treatment of mCRC. The search terms were "cetuximab," "panitumumab," and "colorectal cancer." The deadline of searching was April 2022. Review manager 5.4 software was used to perform the statistical analysis for this meta-analysis. Pooled hazard ratio (HR) with 95% confidence intervals (CI) were calculated to evaluate the overall survival (OS) and progression free survival (PFS) of cetuximab and panitumumab in the treatment of mCRC. RESULTS: There was no significant difference in OS, PFS, and response rate (RR) between cetuximab arm and panitumumab arm (OS: HR = 0.91, 95% CI = 0.81-1.03, p = .14; PFS: HR = 0.92, 95% CI = 0.83-1.02, p = .11; RR: OR = 1.22, 95% CI = 0.96-1.61, p = .14). We also did not observe any statistical difference between both arms in incidence of acneiform rash, severe acneiform rash, diarrhea, and severe diarrhea (acneiform rash: OR = 1.09, 95% CI = 0.84-1.42, p = .51; severe acneiform rash: OR = 1.50, 95% CI = 0.80-2.81, p = .21; diarrhea: OR = 1.08, 95% CI = 0.82-1.42, p = .58; severe diarrhea: OR = 0.90, 95% CI = 0.44-1.84, p = .77). The incidence of paronychia was decreased in the panitumumab arm, but that of hypomagnesemia and severe hypomagnesemia were decreased in the cetuximab arm. (paronychia: OR = 0.74, 95% CI = 0.55-1.00, p = .05; hypomagnesemia: OR = 1.85, 95% CI =1.41-2.41, p < .00001; severe hypomagnesemia: OR = 2.66, 95% CI = 1.52-4.67, p = .0006). CONCLUSION: There was no significant difference in OS, PFS and RR between the cetuximab arm and panitumumab arm in the treatment of mCRC. For adverse reactions, the incidence of paronychia was decreased in the panitumumab arm, and the incidence of hypomagnesemia was deceased in the cetuximab arm.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Exantema , Paroniquia , Neoplasias del Recto , Humanos , Panitumumab/efectos adversos , Cetuximab/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Paroniquia/inducido químicamente , Paroniquia/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Exantema/inducido químicamente , Exantema/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica
9.
J Oncol Pharm Pract ; 29(6): 1374-1380, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36112905

RESUMEN

BACKGROUND: Painful paronychia and pseudopyogenic granuloma (PG) are common adverse drug reactions (ADRs) associated with the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to treat non-small cell lung cancer (NSCLC). Multiple local management approaches have been tested with unsatisfactory results. We have introduced an occlusion therapy technique through which available topical drugs for longer than 2 years. METHODS: Based on the cancer registry and case management system of our hospital, from July 2019 to July 2020, we retrospectively enrolled patients with NSCLC who were treated with EGFR-TKIs and received applications of 0.5% timolol ophthalmic solution (TIMOPTOL XE 0.5%®) combined with a neomycin/tyrothricin ointment (Biomycin®) using the occlusion method to treat paronychia or PG. RESULTS: A total of 22 patients were enrolled, with a mean age of 66.5 years, most of whom were women (72.7%). Periungual lesion-related pain was reported by all patients, and periungual bleeding and PG were reported in 14% (3/22) and 64% (14/22) of patients, respectively. After the occlusion therapy application of timolol ophthalmic solution combined with neomycin/tyrothricin ointment twice daily, the overall response rate was 83.3%, including complete response in 18% (4/22) of cases and partial response in 68% (15/22) of cases. CONCLUSION: We presented an occlusion method using available topical beta-blockers and antibiotic ointment for EGFR-TKI-induced paronychia and PG in Taiwan. The result is favorable. Further randomized control trial is urgent to validate our findings.


Asunto(s)
Hiperplasia Angiolinfoide con Eosinofilia , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Paroniquia , Humanos , Femenino , Anciano , Masculino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Timolol/efectos adversos , Hiperplasia Angiolinfoide con Eosinofilia/inducido químicamente , Hiperplasia Angiolinfoide con Eosinofilia/tratamiento farmacológico , Estudios Retrospectivos , Antibacterianos/efectos adversos , Paroniquia/inducido químicamente , Paroniquia/tratamiento farmacológico , Pomadas/efectos adversos , Taiwán , Inhibidores de Proteínas Quinasas/efectos adversos , Neomicina/efectos adversos , Receptores ErbB , Tirotricina/efectos adversos , Soluciones Oftálmicas/efectos adversos , Mutación
10.
Medicine (Baltimore) ; 101(42): e31208, 2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-36281135

RESUMEN

The development of targeted therapy has improved treatment outcomes for patients with non-small cell lung cancer (NSCLC). However, paronychia, a common adverse effect of targeted therapy, remains burdensome. Although conservative treatments for paronychia have been well reported in the literature, studies on the efficacy of surgical partial matricectomy for paronychia, are scarce. This study aimed to evaluate the effect of surgical partial matricectomy in targeted therapy-induced paronychia in patients with NSCLC. This retrospective cohort study included 11 patients with a total of 18 lesions on the big toes. Data on lung cancer stages, types and duration of targeted therapy, onset of paronychia, pain scale scores, conservative treatments, course of matricectomy, paronychia-free interval after matricectomy, and wound condition were collected from medical records. The Wilcoxon signed-rank test was used for analysis. The mean pain scale score after matricectomy was significantly lower than that after conservative treatments (1.00 ± 0.00 vs 2.94 ± 0.87; P < .001) and before treatment (1.00 ± 0.00 vs 3.06 ± 0.80; P < .001). The mean duration of matricectomy was significantly shorter than that of conservative treatments (3.22 ± 1.00 vs 56.56 ± 52.29 weeks; P < .001). Surgical partial matricectomy is an effective and enduring intervention for targeted therapy-related paronychia. It provides a shorter course of treatment, reduced pain, and improved appearance of the healed wound. Furthermore, surgical partial matricectomy could result in a better quality of life during targeted therapy than that of conservative treatments.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Paroniquia , Humanos , Estudios Retrospectivos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Calidad de Vida , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Paroniquia/inducido químicamente , Paroniquia/cirugía , Dolor
11.
Lung Cancer ; 173: 116-123, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36198244

RESUMEN

CONTEXTE: The Epidermal Growth Factor Receptor (EGFR) is mutated in 10-15% of patients with lung adenocarcinoma. At metastatic stage EGFR tyrosine kinase inhibitors (TKIs) are used front line for patients harboring targetable mutations. Novel anti-EGFR therapies are being developed. Amivantamab is a bispecific anti-EGFR and anti-MET antibody with expected skin toxicities. OBJECTIVE: We developed here guidelines for prevention and treatment of cutaneous toxicities under amivantamab according to our experience at Institut Curie. MATERIEL & METHOD: The first patients with metastatic lung cancer harboring EGFR Exon20ins mutation, included in the phase 1 CHRYSALIS trial and cured at Institute Curie from November 1st 2019 until December 31st 2021 were selected for this work. Retrospectively, all cutaneous adverse events were registered and classified according to the CTCAE 6.0 classification, and actions we implemented to minimize and treat these adverse events were collected. We then developed guidelines based on these datas. RESULTS: A total of seven patients started amivantamab as monotherapy. The two most frequent dermatological adverse events were: acneiform rash and paronychia (100 % of patients). Other adverse events presented by the patients were reported: modification of hair growth with hypertrichosis in 50 % of men (n = 1/2) and hirsutism in 80 % of women (n = 4/5); skin abrasion of the scalp in 71 % (n = 5/7); and skin fissure in 57 % (n = 4/7). We recommend first a rigorous inspection of the skin and teguments to determine the risk rate to have dryer skin under treatment; second a prevention of paronychia/acneiform rash/and skin fissures with prophylactic tetracycline, skin moisturizing, and hygienic measures starting at least 14 days before treatment initiation; third a particular attention to the psychological impact of skin toxicities with access to psychological support. CONCLUSION: We propose here guidelines for the management of dermatological toxicities under amivantamab with a multidisciplinary approach for the proactive management of cutaneous toxicities with a focus on preventive actions.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Inhibidores de Proteínas Quinasas , Enfermedades de la Piel , Femenino , Humanos , Masculino , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Exantema/inducido químicamente , Exantema/prevención & control , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Paroniquia/inducido químicamente , Paroniquia/prevención & control , Inhibidores de Proteínas Quinasas/toxicidad , Enfermedades de la Piel/inducido químicamente , Enfermedades de la Piel/prevención & control
12.
Zhongguo Fei Ai Za Zhi ; 25(7): 493-500, 2022 Jul 20.
Artículo en Chino | MEDLINE | ID: mdl-35899447

RESUMEN

BACKGROUND: Epidermal growth factor receptor (EGFR) and cellular-mesenchymal to epithelial transition factor (c-Met) are widely expressed on cancer cells. There is a synergistic effect of EGFR and HGF/c-Met pathways on proliferation, downstream activation of signal transduction and an additive effect. Studies show that combination of both signaling pathways could potentially be targeted in a synergistic fashion. Amivantamab, a bispecific monoclonal antibody targeting EGFR and c-Met, yielded robust and durable responses in a variety of clinicals trials. However, few researches have reported its efficacy in Chinese non-small cell lung cancer (NSCLC) patients. This study was conducted to evaluate the effectiveness and tolerance of Amivantamab in NSCLC patients with EGFR/MET gene abnormalities at Peking University Cancer Hospital. METHODS: The study enrolled NSCLC patients who received Amivantamab in our hospital between August 2020 and December 2021, and analyzed the response, survival, and treatment-related adverse events. RESULTS: Fifteen patients were enrolled in this research, and six of them received Amivantamab treatment and the other nine patients received Amivantamab plus Lazertinib treatment. The rates of partial response (PR), stable disease (SD), and progressive disease (PD) were 46.7% (7/15), 46.7% (7/15) and 6.7% (1/15), respectively. The overall response rate (ORR) and disease control rate (DCR) were 28.6% (2/7) and 100.0% (7/7) in seven patients with EGFR exon 20 insertion, respectively. The ORR and DCR were 40.0% (2/5) and 100.0% (5/5) in five post-osimertinib EGFR-mutant patients, respectively. After a median follow-up of 8.7 months, the median progression-free survival and overall survival were not reached. The most common treatment-related adverse events were rash (86.7%), paronychia (80.0%), and infusion-related reactions (60.0%), and most of them were graded as 1 to 2. Grade 3 to 4 adverse events included rash (33.3%), alanine aminotransferase elevation (13.3%), gamma-glutamyl transpeptidase elevation (13.3%), peripheral edema (6.7%), thromboembolism (6.7%), interstitial lung disease (6.7%), and thrombocytopenia (6.7%). CONCLUSIONS: Amivantamab was effective in Chinese NSCLC patients with EGFR exon 20 insertion and post-Osimertinib EGFR-mutant patients, similar to the results of clinical trials conducted in western countries. Amivantamab was well tolerated and emphases should be put on adverse events such as rash, paronychia, and infusion-related reactions.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Exantema , Neoplasias Pulmonares , Paroniquia , Anticuerpos Biespecíficos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Exantema/inducido químicamente , Exantema/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Paroniquia/inducido químicamente , Paroniquia/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico
15.
J Dermatolog Treat ; 33(4): 1990-1994, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33961534

RESUMEN

We evaluated the efficacy and safety of red light LED as an adjuvant treatment for epidermal growth factor receptor inhibitor-induced paronychia. Eight patients were recruited in this randomized, single-blinded controlled trial. They were randomized to receive red-light on one hand or foot 2-3 times/week for 6 weeks while the contralateral side served as controls. The standard treatments were continued. Erythema and lesion elevation observed by Anthera® 3D, severity and pain scores were obtained at weeks 0, 2, 4, 6, and 8. The red light group showed significantly lower erythema, severity, and pain scores at weeks 4, 6, and 8. The elevation was significantly lower in the red light group at every follow-up visit. No adverse events occurred. Red light therapy may be an option as adjunctive treatment for EGFRi-induced paronychia.


Asunto(s)
Paroniquia , Fototerapia , Inhibidores de Proteínas Quinasas , Receptores ErbB/antagonistas & inhibidores , Eritema/etiología , Eritema/terapia , Humanos , Dolor/etiología , Paroniquia/inducido químicamente , Paroniquia/complicaciones , Paroniquia/terapia , Fototerapia/métodos , Inhibidores de Proteínas Quinasas/efectos adversos , Método Simple Ciego
16.
J Clin Oncol ; 39(30): 3391-3402, 2021 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-34339292

RESUMEN

PURPOSE: Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (Exon20ins) mutations exhibits inherent resistance to approved tyrosine kinase inhibitors. Amivantamab, an EGFR-MET bispecific antibody with immune cell-directing activity, binds to each receptor's extracellular domain, bypassing resistance at the tyrosine kinase inhibitor binding site. METHODS: CHRYSALIS is a phase I, open-label, dose-escalation, and dose-expansion study, which included a population with EGFR Exon20ins NSCLC. The primary end points were dose-limiting toxicity and overall response rate. We report findings from the postplatinum EGFR Exon20ins NSCLC population treated at the recommended phase II dose of 1,050 mg amivantamab (1,400 mg, ≥ 80 kg) given once weekly for the first 4 weeks and then once every 2 weeks starting at week 5. RESULTS: In the efficacy population (n = 81), the median age was 62 years (range, 42-84 years); 40 patients (49%) were Asian, and the median number of previous lines of therapy was two (range, 1-7). The overall response rate was 40% (95% CI, 29 to 51), including three complete responses, with a median duration of response of 11.1 months (95% CI, 6.9 to not reached). The median progression-free survival was 8.3 months (95% CI, 6.5 to 10.9). In the safety population (n = 114), the most common adverse events were rash in 98 patients (86%), infusion-related reactions in 75 (66%), and paronychia in 51 (45%). The most common grade 3-4 adverse events were hypokalemia in six patients (5%) and rash, pulmonary embolism, diarrhea, and neutropenia in four (4%) each. Treatment-related dose reductions and discontinuations were reported in 13% and 4% of patients, respectively. CONCLUSION: Amivantamab, via its novel mechanism of action, yielded robust and durable responses with tolerable safety in patients with EGFR Exon20ins mutations after progression on platinum-based chemotherapy.


Asunto(s)
Anticuerpos Biespecíficos/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Biespecíficos/efectos adversos , Anticuerpos Biespecíficos/farmacocinética , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/farmacocinética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/secundario , Diarrea/inducido químicamente , Progresión de la Enfermedad , Erupciones por Medicamentos/etiología , Exones , Femenino , Humanos , Hipopotasemia/inducido químicamente , Reacción en el Punto de Inyección/etiología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutagénesis Insercional , Neutropenia/inducido químicamente , Compuestos Organoplatinos/uso terapéutico , Paroniquia/inducido químicamente , Supervivencia sin Progresión , Embolia Pulmonar/inducido químicamente , Retratamiento
17.
Dermatol Surg ; 47(6): 775-779, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34029250

RESUMEN

BACKGROUND: Paronychia is a common toxicity associated with targeted anticancer therapies. Antibiotics and steroids are the standard treatments for severe paronychia, yet they are often inadequate, prolonging the patient's suffering and resulting in changes to effective cancer therapy. OBJECTIVE: This article describes the clinical course of drug-induced paronychia and attempts to identify circumstances under which nail surgery may be beneficial. MATERIALS AND METHODS: This is a retrospective case series from a single institution's electronic medical record for patients on paronychia-inducing anticancer therapies with nail disease visit diagnosis codes. RESULTS: The authors identified 36 nail procedures performed on 12 patients, all of whom were managed with conservative steroid and antibiotic therapy with varying degrees of improvement; however, no further improvement was seen after 90 days. Partial matricectomy, nail avulsion, debridement/clipping, and incision and drainage were performed with resolution rates of 100% (11/11), 38.5% (5/13), 12.5% (1/8), and 0% (0/4), respectively. The average time to surgical intervention was 196 days, and the average time to resolution was 268 days. CONCLUSION: This series highlights the prolonged course of severe drug-induced paronychia and the importance of surgical intervention to reduce pain and impact on cancer treatment. Partial matricectomy should be considered for paronychia unresponsive to conservative therapy by 3 months.


Asunto(s)
Antineoplásicos/efectos adversos , Drenaje/métodos , Neoplasias/tratamiento farmacológico , Paroniquia/cirugía , Adulto , Anciano , Antibacterianos/administración & dosificación , Terapia Combinada , Femenino , Glucocorticoides/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida/efectos adversos , Terapia Molecular Dirigida/métodos , Uñas/efectos de los fármacos , Uñas/inmunología , Uñas/patología , Paroniquia/inducido químicamente , Paroniquia/diagnóstico , Paroniquia/inmunología , Estudios Retrospectivos , Piel/efectos de los fármacos , Piel/inmunología , Piel/patología , Resultado del Tratamiento
18.
Cancer Med ; 10(11): 3556-3564, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33939292

RESUMEN

PURPOSE: To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib. METHODS: We report on six patients with NF-1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively. RESULTS: Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4-28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life-threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1-2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy. CONCLUSION: Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF-1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients.


Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Neurofibroma Plexiforme/tratamiento farmacológico , Neurofibromatosis 1/tratamiento farmacológico , Piridonas/administración & dosificación , Pirimidinonas/administración & dosificación , Adolescente , Antineoplásicos/efectos adversos , Neoplasias Encefálicas/diagnóstico por imagen , Colombia Británica , Niño , Preescolar , Ensayos de Uso Compasivo , Dermatitis Atópica/inducido químicamente , Resistencia a Antineoplásicos , Femenino , Glioma/diagnóstico por imagen , Humanos , Lactante , Masculino , Neurofibroma Plexiforme/diagnóstico por imagen , Neurofibromatosis 1/diagnóstico por imagen , Paroniquia/inducido químicamente , Piridonas/efectos adversos , Pirimidinonas/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento
20.
J Am Acad Dermatol ; 84(6): 1554-1561, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32682884

RESUMEN

BACKGROUND: Treatment with BRAF inhibitors (BRAFI) and MEK inhibitors (MEKI) causes cutaneous reactions in children, limiting dosing or resulting in treatment cessation. The spectrum and severity of these reactions is not defined. OBJECTIVE: To determine the frequency and spectrum of cutaneous reactions in children receiving BRAFI and MEKI and their effects on continued therapy. METHODS: A multicenter, retrospective study was conducted at 11 clinical sites in the United States and Canada enrolling 99 children treated with BRAFI and/or MEKI for any indication from January 1, 2012, to January 1, 2018. RESULTS: All children in this study had a cutaneous reaction; most had multiple, with a mean per patient of 3.5 reactions on BRAFI, 3.7 on MEKI, and 3.4 on combination BRAFI/MEKI. Three patients discontinued treatment because of a cutaneous reaction. Treatment was altered in 27% of patients on BRAFI, 39.5% on MEKI, and 33% on combination therapy. The cutaneous reactions most likely to alter treatment were dermatitis, panniculitis, and keratosis pilaris-like reactions for BRAFI and dermatitis, acneiform eruptions, and paronychia for MEKI. CONCLUSIONS: Cutaneous reactions are common in children receiving BRAFI and MEKI, and many result in alterations or interruptions in oncologic therapy. Implementing preventative strategies at the start of therapy may minimize cutaneous reactions.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Erupciones por Medicamentos/epidemiología , Neoplasias/tratamiento farmacológico , Paroniquia/epidemiología , Inhibidores de Proteínas Quinasas/efectos adversos , Adolescente , Canadá/epidemiología , Niño , Preescolar , Erupciones por Medicamentos/diagnóstico , Erupciones por Medicamentos/etiología , Femenino , Humanos , Lactante , Masculino , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Paroniquia/inducido químicamente , Proteínas Proto-Oncogénicas B-raf/antagonistas & inhibidores , Estudios Retrospectivos , Estados Unidos/epidemiología
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