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1.
ESMO Open ; 9(4): 102996, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38613911

RESUMEN

BACKGROUND: Targeted therapy (TT) with encorafenib and cetuximab is the current standard for patients with BRAFV600E-mutated metastatic colorectal cancer (mCRC) who received one or more prior systemic treatments. However, the median progression-free survival (mPFS) is ∼4 months, and little is known about the possibility of administering subsequent therapies, their efficacy, and clinicopathological determinants of outcome. METHODS: A real-world dataset including patients with BRAFV600E-mutated mCRC treated with TT at 21 Italian centers was retrospectively interrogated. We assessed treatments after progression, attrition rates, and outcomes. RESULTS: Of the 179 patients included, 85 (47%), 32 (18%), and 7 (4%) received one, two, or three lines of treatment after TT, respectively. Those receiving TT in the second line were more likely to receive at least one subsequent therapy (53%), as compared with those treated with TT in the third line or beyond (30%; P < 0.0001), and achieved longer postprogression survival (PPS), also in a multivariate model (P = 0.0001). Among 62 patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) tumors receiving one or more lines of treatment after second-line TT, combinatory chemotherapy ± anti-vascular endothelial growth factor (anti-VEGF) was associated with longer PFS and PPS as compared with trifluridine-tipiracil or regorafenib (mPFS: 2.6 versus 2.0 months, P = 0.07; PPS: 6.5 versus 4.4 months, P = 0.04). CONCLUSIONS: Our real-world data suggest that TT should be initiated as soon as possible after the failure of first-line treatment in BRAFV600E-mutated mCRC. Among patients with pMMR/MSS tumors, combinatory chemotherapy ± anti-VEGF appears the preferred treatment choice after TT failure.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Carbamatos , Cetuximab , Neoplasias Colorrectales , Mutación , Proteínas Proto-Oncogénicas B-raf , Sulfonamidas , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Cetuximab/uso terapéutico , Cetuximab/farmacología , Masculino , Femenino , Proteínas Proto-Oncogénicas B-raf/genética , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Carbamatos/uso terapéutico , Carbamatos/farmacología , Sulfonamidas/uso terapéutico , Sulfonamidas/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Progresión de la Enfermedad , Supervivencia sin Progresión , Adulto , Anciano de 80 o más Años , Metástasis de la Neoplasia , Italia
2.
ESMO Open ; 7(3): 100506, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35696748

RESUMEN

BACKGROUND: Encorafenib plus cetuximab with or without binimetinib showed increased objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared with chemotherapy plus anti-EGFR in previously treated patients with BRAF V600E-mutated (mut) metastatic colorectal cancer (mCRC). Although no formal comparison was planned, addition of binimetinib to encorafenib plus cetuximab did not provide significant efficacy advantage. PATIENTS AND METHODS: This real-life study was aimed at evaluating safety, activity, and efficacy of encorafenib plus cetuximab with or without binimetinib in patients with BRAF V600E-mut mCRC treated at 21 Italian centers within a nominal use program launched in May 2019. RESULTS: Out of 133 patients included, 97 (73%) received encorafenib plus cetuximab (targeted doublet) and 36 (27%) the same therapy plus binimetinib (targeted triplet). Most patients had Eastern Cooperative Group Performance Status (ECOG-PS) of 0 or 1 (86%), right-sided primary tumor (69%), and synchronous disease (66%). Twenty (15%) tumors were DNA mismatch repair deficiency (dMMR)/microsatellite instability (MSI)-high. As many as 44 (34%) patients had received two or more prior lines of therapy, 122 (92%) were previously exposed to oxaliplatin, and 109 (82%) to anti-vascular endothelial growth factor (anti-VEGF). Most frequent adverse events were asthenia (62%) and anti-EGFR-related skin rash (52%). Any grade nausea (P = 0.03), vomiting (P = 0.04), and diarrhea (P = 0.07) were more frequent with the triplet therapy, while melanocytic nevi were less common (P = 0.06). Overall, ORR and disease control rate (DCR) were 23% and 69%, respectively, with numerically higher rates in the triplet group (ORR 31% versus 17%, P = 0.12; DCR 78% versus 65%, P = 0.23). Median PFS and OS were 4.5 and 7.2 months, respectively. Worse ECOG-PS, peritoneal metastases, and more than one prior treatment were independent poor prognostic factors for PFS and OS. Clonality of BRAF mutation measured as adjusted mutant allele fraction in tumor tissue was not associated with clinical outcome. CONCLUSIONS: Our real-life data are consistent with those from the BEACON trial in terms of safety, activity, and efficacy. Patients in good general condition and not heavily pretreated are those more likely to derive benefit from the targeted treatment.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bencimidazoles , Carbamatos , Cetuximab/efectos adversos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Humanos , Proteínas Proto-Oncogénicas B-raf/genética , Sulfonamidas
3.
Eur Rev Med Pharmacol Sci ; 25(2): 923-931, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33577047

RESUMEN

OBJECTIVE: Achieving glycemic target is paramount to control diabetes mellitus (DM) and reduce micro-vascular and macro-vascular complications. Despite the mostly recent-developed drugs, most patients still show an above desired glycated hemoglobin (HbA1c) level due to DM complex pathophysiology, therapeutic and dietary compliance and clinical inertia in introducing or intensifying insulin therapy. To support the promising results of clinical trials on the effectiveness and safety of the degludec/liraglutide combination (IDegLira) in type 2 DM patients with C-peptide values >1 ng/ml who were previously treated with basal-bolus multiple daily-dose insulin injections. PATIENTS AND METHODS: This observational, prospective and non-randomized trial enrolled type 2 DM patients referred to our outpatient clinic between January 2019 and December 2019, who were shifted from multiple daily-dose insulin injection therapy to degludec/liraglutide combination as per the physician's decision. The main assessment was HbA1c variation at 6 months from baseline. Secondary assessments included variation in fasting glycemia, routine anthropometric assessments, blood chemistry, blood pressure and patients' quality of life (measured by the Diabetes Treatment Satisfaction Questionnaire [DTSQ]), from baseline to 6 months. RESULTS: HbA1c (8.4 vs. 7.4%; p<0.0001) and body weight (94.1 vs. 93 kg; p<0.0001) were significantly lower after 6 months for patients on the degludec/liraglutide combination. A similar trend was observed in fasting glycemia levels (159 vs. 125 mg/dl; p<0.0001). An improved glycemic control was achieved with degludec/liraglutide despite a reduction in total daily insulin units (42 U at 6 months vs. 22 U at baseline; p<0.0001). In addition, higher scores in the DTSQ were registered after 6 months on degludec/liraglutide (mean score: 27 vs. 20; p<0.0001). The combination therapy also proved more convenient than basal-bolus therapy in terms of costs, with an average per-patient cost difference of €-0.41±0.59/die (p<0.0001). CONCLUSIONS: These real-world findings show that degludec/liraglutide seems to be more effective than basal-bolus insulin in achieving glycemic control, allowing cost sustainability and improving patient satisfaction.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina de Acción Prolongada/uso terapéutico , Liraglutida/uso terapéutico , Anciano , Peso Corporal , Estudios de Cohortes , Diabetes Mellitus Tipo 2/diagnóstico , Combinación de Medicamentos , Ayuno , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipoglucemia/diagnóstico , Masculino , Persona de Mediana Edad , Estudios Prospectivos
4.
Eur Rev Med Pharmacol Sci ; 18(14): 2013-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25027340

RESUMEN

OBJECTIVES: With the purpose of evaluating the role of oxidative stress (OS) in male idiopatic osteoporosis, we have evaluated plasma total antioxidant capacity (TAC) in patients classified according to age (< 65 or ≥ 65 yrs), with normal hormone values and in age-matched healthy control subjects. PATIENTS AND METHODS: TAC was evaluated with a colorimetric method, using the system metamyoglobin-H2O2 and the chromogen ABTS; the latency time (LAG, sec) in the appearance of ABTS radical species is proportional to antioxidant content of the system. RESULTS: We found slightly increased LAG values in middle-aged patients, compared with age-matched controls, probably expression of a compensatory mechanism to OS; on the contrary aged patients showed significantly lower LAG values in comparison with age-matched controls, suggesting a defective compensatory mechanism and, therefore, a risk for oxidative damage. CONCLUSIONS: OS could be a possible mechanism underlying male osteoporosis, both in middle-aged and aged patients, but compensatory mechanisms seem to be defective in the last group.


Asunto(s)
Antioxidantes/metabolismo , Osteoporosis/sangre , Adulto , Factores de Edad , Anciano , Estudios de Casos y Controles , Colorimetría/métodos , Humanos , Masculino , Persona de Mediana Edad
5.
Int J Endocrinol ; 2013: 607939, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24363671

RESUMEN

Among treatments proposed for idiopathic male infertility, antiestrogens, like tamoxifen, play a possible role. On the other hand, oxidative stress is a mechanism well recognized for deleterious effects on spermatozoa function. After reviewing the literature on the effects of estrogens in modulation of antioxidant systems, in both sexes, and in different in vivo and in vitro models, we suggest, also on the basis of personal data, that a tamoxifen treatment could be active via an increase in seminal antioxidants.

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