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1.
Brasília; CONITEC; ago. 2024.
Non-conventional in Spanish | BRISA/RedTESA | ID: biblio-1572379

ABSTRACT

INTRODUÇÃO: O carcinoma diferenciado da tireoide (CDT) é a forma mais comum de câncer da tireoide. O tratamento consiste no procedimento cirúrgico para a remoção do tumor e, em alguns casos, da tireoide inteira (tireoidectomia total). Porém, pacientes com doença em progressão são candidatos à terapia sistêmica, com utilização de inibidores de tirosina quinase como sorafenibe e lenvatinibe. Estes fármacos atuam no processo de angiogênese necessária para a formação do tumor e suas metástases. Desta forma, o objetivo deste relatório foi avaliar a eficácia, efetividade e impacto orçamentário de sorafenibe e lenvatinibe para o tratamento de adultos com diagnóstico de CDT localmente avançado e/ou metastático, refratário ao iodo, progressivo, no SUS. PERGUNTA DE PESQUISA: O sorafenibe e o lenvatinibe são mais eficazes e seguros para o tratamento de pacientes com diagnóstico de CDT localmente avançado e/ou metastático, refratário ao iodo, progressivo, quando comparado à quimioterap


Subject(s)
Humans , Thyroid Neoplasms/drug therapy , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Sorafenib/therapeutic use , Iodine/adverse effects , Neoplasm Metastasis/drug therapy , Unified Health System , Brazil , Cost-Benefit Analysis/economics
2.
Endocrine ; 85(2): 817-826, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38772990

ABSTRACT

PURPOSE: To evaluate objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) associated with tyrosine kinase inhibitors (TKIs) in patients with radioiodine refractory differentiated thyroid cancer (RR-DTC). Additionally, to compare: (i) ORR and PFS among patients treated with lenvatinib and sorafenib; (ii) ORR and PFS among patients receiving lenvatinib as first-line vs. second-line and; (iii) adverse effects (AEs) observed in patients treated with these medications. METHODS: Retrospective analysis of RR-DTC adult patients treated with TKIs at the Division of Endocrinology, Hospital de Clinicas, University of Buenos Aires (March 2011-November 2023). RESULTS: Among 43 patients included in the study, 32 received sorafenib (30 as first-line and 2 as second-line), while 29 received lenvatinib (12 as first-line and 17 as second-line). The median PFS and OS for the entire cohort were 32.7 and 39.0 months, respectively. Lenvatinib demonstrated a significantly higher ORR compared to sorafenib (37.9% vs. 9.4%, p = 0.008). However, both drugs exhibited similar median PFS (23.2 vs. 16.0 months, p = 0.419). No significant difference was observed in ORR and PFS between patients receiving first-line vs. second-line lenvatinib. Sorafenib-treated patients experienced higher rates of hand-foot skin syndrome (69% vs. 41%, p = 0.032) and alopecia (25% vs. 3%, p = 0.018), whereas lenvatinib-treated patients had higher rates of proteinuria (31% vs. 0%, p < 0.001) and grade 3 hypertension (31% vs. 9%, p = 0.034). CONCLUSION: TKIs demonstrated efficacy and tolerability comparable to real-world data in RR-DTC. PFS was not statistically different between sorafenib and lenvatinib. Our study will help guide physicians in making informed decisions regarding treatment sequencing with TKIs in these patients.


Subject(s)
Phenylurea Compounds , Protein Kinase Inhibitors , Quinolines , Sorafenib , Thyroid Neoplasms , Humans , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/pathology , Female , Male , Phenylurea Compounds/therapeutic use , Phenylurea Compounds/adverse effects , Middle Aged , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/adverse effects , Retrospective Studies , Sorafenib/therapeutic use , Sorafenib/adverse effects , Quinolines/therapeutic use , Quinolines/adverse effects , Adult , Aged , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Treatment Outcome , Progression-Free Survival , Aged, 80 and over
3.
BMJ Case Rep ; 17(2)2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38378588

ABSTRACT

We present the case of a female patient in her late 70s, diagnosed with widely invasive oncocytic cell carcinoma, with extrathyroidal extension, infiltration into the extrathyroidal muscle, involvement of the sternohyoid muscle and infiltration into the external muscle fibres of the oesophagus. Over the following year, metastases were documented in the lungs, bones and brain. Additionally, there was progression of the locally advanced lesion involving the airway and upper gastrointestinal tract. After considering iodine refractoriness, treatment with sorafenib was initiated. Notably, regression of the locoregional lesion at the cervical level was observed following treatment with the multikinase inhibitor.


Subject(s)
Adenocarcinoma , Thyroid Neoplasms , Humans , Female , Sorafenib/therapeutic use , Thyroid Neoplasms/pathology , Niacinamide/therapeutic use , Phenylurea Compounds/therapeutic use , Thyroid Cancer, Papillary
4.
Int J Mol Sci ; 25(3)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38339037

ABSTRACT

Hepatocellular carcinoma (HCC) is among the main causes of death by cancer worldwide, representing about 80-90% of all liver cancers. Treatments available for advanced HCC include atezolizumab, bevacizumab, sorafenib, among others. Atezolizumab and bevacizumab are immunological options recently incorporated into first-line treatments, along with sorafenib, for which great treatment achievements have been reached. However, sorafenib resistance is developed in most patients, and therapeutical combinations targeting cancer hallmark mechanisms and intracellular signaling have been proposed. In this review, we compiled evidence of the mechanisms of cell death caused by sorafenib administered alone or in combination with valproic acid and metformin and discussed them from a molecular perspective.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Metformin , Humans , Carcinoma, Hepatocellular/metabolism , Sorafenib/pharmacology , Sorafenib/therapeutic use , Liver Neoplasms/metabolism , Valproic Acid/pharmacology , Valproic Acid/therapeutic use , Bevacizumab , Metformin/pharmacology , Metformin/therapeutic use , Cell Death
5.
World J Gastroenterol ; 29(17): 2571-2599, 2023 May 07.
Article in English | MEDLINE | ID: mdl-37213397

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most lethal malignant tumours worldwide. The mortality-to-incidence ratio is up to 91.6% in many countries, representing the third leading cause of cancer-related deaths. Systemic drugs, including the multikinase inhibitors sorafenib and lenvatinib, are first-line drugs used in HCC treatment. Unfortunately, these therapies are ineffective in most cases due to late diagnosis and the development of tumour resistance. Thus, novel pharmacological alternatives are urgently needed. For instance, immune checkpoint inhibitors have provided new approaches targeting cells of the immune system. Furthermore, monoclonal antibodies against programmed cell death-1 have shown benefits in HCC patients. In addition, drug combinations, including first-line treatment and immunotherapy, as well as drug repurposing, are promising novel therapeutic alternatives. Here, we review the current and novel pharmacological approaches to fight HCC. Preclinical studies, as well as approved and ongoing clinical trials for liver cancer treatment, are discussed. The pharmacological opportunities analysed here should lead to significant improvement in HCC therapy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Sorafenib/therapeutic use , Antibodies, Monoclonal/therapeutic use , Molecular Targeted Therapy , Immunotherapy
6.
J Med Econ ; 26(1): 731-741, 2023.
Article in English | MEDLINE | ID: mdl-37139828

ABSTRACT

AIMS: Hepatocellular carcinoma (HCC) is a severe condition with poor prognosis that places a significant burden on patients, caregivers, and healthcare systems. Selective internal radiation therapy (SIRT) is a treatment available to patients with HCC which addresses some of the limitations of alternative treatment options. A cost-effectiveness analysis was undertaken into the use of SIRT using Y-90 resin microspheres for the treatment of unresectable intermediate- and late-stage HCC in Brazil. MATERIALS AND METHODS: A partitioned-survival model was developed, including a tunnel state for patients downstaged to receive treatments with curative intent. Sorafenib was the selected comparator, a common systemic treatment in Brazil and for which comparative evidence exists. Clinical data were extracted from published sources of pivotal trials, and effectiveness was measured in quality-adjusted life-years (QALYs) and life-years (LYs). The analysis was conducted from the Brazilian private payer perspective and a lifetime horizon was implemented. Comprehensive sensitivity analyses were conducted. RESULTS: LYs and QALYs were higher for SIRT with Y-90 resin microspheres versus sorafenib (0.27 and 0.20 incremental LYs and QALYs, respectively) and costs were slightly higher for SIRT (R$15,864). The base case incremental cost-effectiveness ratio (ICER) was R$77,602 per QALY. The ICER was mostly influenced by parameters defining the sorafenib overall survival curve and SIRT had a 73% probability of being cost-effective at a willingness-to-pay threshold of R$135,761 per QALY (3-times the per-capita gross domestic product in Brazil). Overall, sensitivity analyses confirmed the robustness of the results indicating that SIRT with Y-90 resin microspheres is cost-effective compared with sorafenib. LIMITATIONS: A rapidly evolving treatment landscape in Brazil and worldwide, and the lack of local data for some variables were the main limitations. CONCLUSIONS: SIRT with Y-90 resin microspheres is a cost-effective option compared with sorafenib in Brazil.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Sorafenib/therapeutic use , Cost-Benefit Analysis , Yttrium Radioisotopes , Brazil , Liver Neoplasms/drug therapy , Microspheres
7.
World J Gastroenterol ; 28(28): 3595-3607, 2022 Jul 28.
Article in English | MEDLINE | ID: mdl-36161041

ABSTRACT

Hepatocellular carcinoma (HCC) is among the most common cancers and it is a major cause of cancer-related deaths. Non-alcoholic fatty liver disease (NAFLD) affects approximately one fourth of individuals worldwide and it is becoming one of the most important causes of HCC. The pathogenic mechanisms leading to NAFLD-related HCC are complex and not completely understood. However, metabolic, fibrogenic, oncogenic, inflammatory and immunological pathways seem to be involved. First-line therapy of advanced HCC has recently undergone major changes, since the combination of atezolizumab and bevacizumab was proven to increase survival when compared to sorafenib. Other immune-oncology drugs are also demonstrating promising results in patients with advanced HCC when compared to traditional systemic therapy. However, initial studies raised concerns that the advantages of immunotherapy might depend on the underlying liver disease, which seems to be particularly important in NAFLD-related HCC, as these tumors might not benefit from it. This article will review the mechanisms of NAFLD-related hepatocarcinogenesis, with an emphasis on its immune aspects, the efficacy of traditional systemic therapy for advanced NAFLD-related HCC, and the most recent data on the role of immunotherapy for this specific group of patients, showing that the management of this condition should be individualized and that a general recommendation cannot be made at this time.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Bevacizumab/therapeutic use , Carcinogenesis , Humans , Immunotherapy/adverse effects , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/therapy , Sorafenib/therapeutic use
8.
Lima; INEN; mayo 2022.
Non-conventional in Spanish | BRISA/RedTESA | ID: biblio-1428547

ABSTRACT

INTRODUCCIÓN: Hepatocarcinoma es la neoplasia con la séptima incidencia más frecuente y la cuarta mayor mortalidad a nivel mundial, según Globocan 2020. El carcinoma hepatocelular es altamente letal, con opciones de tratamiento limitadas. La edad promedio tiene un rango etario entre 60-70 años, pero varía según la distribución geográfica. Es más frecuente en países en vías de desarrollo y es causado principalmente por el virus de la hepatitis B, virus de la hepatitis C, esteatohepatitis no alcohólica y alcoholismo. El 80-90% de pacientes con hepatocarcinoma tiene cirrosis hepática. Los criterios Child-Turcotte-Pugh permiten evaluar el grado de severidad de la cirrosis. La sobrevida alcanzada al año en los pacientes con Child-Pugh A, B y C es del 95%, 80% y 45%, respectivamente. El tratamiento de los pacientes con hepatocarcinoma y cirrosis hepática significa un reto médico, debido a las comorbilidades de fondo, insuficiencia hepática y mayor riesgo de infecciones. TECNOLOGÍA: Sorafenib es un inhibidor oral multiquinasa que actúa a nivel de las células endoteliales e inhibe la proliferación celular a través de la inhibición del RAF quinasa serina/treonina. Ha sido empleado en el tratamiento de neoplasias malignas, incluido hepatocarcinoma. MÉTODOS: Se plantea la pregunta PICO: "¿En los pacientes con diagnóstico de Hepatocarcinoma no operable o metastásico, sin tratamiento sistémico previo, con CHILD-PUGH Clase A, ¿Cuál es la eficacia y seguridad de sorafenib en comparación con Placebo?". Se tomaron como objetivos de estudio la sobrevida libre de progresión (SLP), sobrevida global (SG) y toxicidad. En base a la pregunta PICO, se realizó una búsqueda sistemática en MEDLINE, COCHRANE, BRISA y TRIP DATABASE. DISCUSIÓN: Hepatocarcinoma es la séptima neoplasia con mayor incidencia y la cuarta con mayor mortalidad a nivel mundial, según Globocan 2020. El carcinoma hepatocelular es altamente letal, con opciones de tratamiento limitadas. La edad promedio tiene un rango etario entre 60-70 años, pero varía según la distribución geográfica. Es más frecuente en países en vías de desarrollo y es causado principalmente por el virus de la hepatitis B, virus de la hepatitis C, esteatohepatitis no alcohólica y alcoholismo. El 80-90% de pacientes con hepatocarcinoma tiene cirrosis hepática. Los criterios Child-TurcottePugh permiten evaluar el grado de severidad de la cirrosis. La sobrevida alcanzada al año en los pacientes con Child-Pugh A, B y C es del 95%, 80% y 45%, respectivamente. El tratamiento de los pacientes con hepatocarcinoma y cirrosis hepática significa un reto médico. Sorafenib es un inhibidor oral multiquinasa que actúa a nivel de las células endoteliales e inhibe la proliferación celular a través de la inhibición del RAF quinasa serina/treonina. La experiencia en el INEN apunta que Sorafenib fue empleado en 03 pacientes durante el año 2019, 20 pacientes en el 2020, 20 pacientes en el 2021 y 03 paciente durante lo que va del año 2022 (Gráfico N°3). Veinte pacientes con CHC recibieron sorafenib durante el año 2021. Todos los pacientes tenían diagnostico CHC irresecablemetastásico, Child Pugh A, durante el año 2021. El 25% eran mujeres, con edad media de 53.5 años (40% eran menores de 40 años). La media de tiempo de tratamiento fue 6.15 meses, similar al obtenido en el estudio SHARP. El 25% recibió entre 11-13 cursos de sorafenib. El 16% continúan sorafenib hasta la fecha. Con respecto a la toxicidad; se reportaron: astenia, dolor abdominal, descamación, anemia, plaquetopenia, mucositis, síndrome mano-pie, hiperbilirrubinemia, hipertransaminasemia, diarrea y náuseas. La toxicidad grado 3-4 reportada fue: dérmica, anemia e hipertransaminasemia. Un paciente descontinuo terapia por toxicidad dérmica grado 3, cuatro pacientes descontinuaron terapia por descompensación de cirrosis hepática. Un paciente descontinuo terapia por perderse de vista tras pandemia por covid-19. El 80% (16) descontinuó por progresión de enfermedad. CONCLUSIONES: El carcinoma hepatocelular es una de las neoplasias con mayor mortalidad en nuestro país. Las opciones de tratamiento para carcinoma hepatocelular irresecable/metastásico son limitadas o inaccesibles en nuestro país. Evaluaciones de tecnología sanitaria y guías de práctica clínica internacionales recomiendan el empleo de sorafenib en pacientes con carcinoma hepatocelular metastásico/irresecable, Child Pugh A, ECOG 0-2. 02 RS/MA es seguro y eficaz (mejora estadísticamente la SLP y SG) con sorafenib en comparación con placebo en pacientes con carcinoma hepatocelular metastásico/irresecable, Child Pugh A, previamente no tratados, ECOG 0-2. 02 ECAs reporta que sorafenib es seguro y eficaz en carcinoma hepatocelular metastásico/irresecable, Child Pugh A, previamente no tratados, ECOG 0-2. Agencias regulatorias internacionales (FDA. EMA) recomiendan el empleo de sorafenib en la población de interés. La experiencia de terapia en el INEN sugiere que el tratamiento con sorafenib es seguro y eficaz en la población de interés. Ante lo presentado y discutido en reunión de la UFETS, se decide aprobar el empleo de Sorafenib en los pacientes con hepatocarcinoma avanzado/irresecable, con buena condición clínica (ECOG 0-1) y Child-Pugh A.


Subject(s)
Humans , Carcinoma, Hepatocellular/drug therapy , Sorafenib/therapeutic use , Efficacy , Cost-Benefit Analysis/economics
9.
JAMA Netw Open ; 4(12): e2136128, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34870682

ABSTRACT

Importance: Immune checkpoint inhibitors (ICIs) have yielded conflicting results in hepatocellular carcinoma (HCC). The overall effect of ICIs compared with standard therapies in unresectable HCC requires more research. Objective: To estimate the efficacy and safety associated with ICIs compared with standard therapies in patients with unresectable HCC. Data Sources: PubMed, Cochrane Library, Web of Science, Latin American and Caribbean Health Sciences Literature, and American Society of Clinical Oncology and European Society of Medical Oncology meeting proceedings were systematically searched. Reference lists from studies selected by electronic searching were manually searched to identify additional relevant studies. The search included literature published or presented from February 2010 to February 2020. Study Selection: From December 2019 to February 2020, independent reviewers evaluated each database, scanning the title, abstract, and keywords of every record retrieved. Full articles were further assessed if the information given suggested that the study was a randomized clinical trial (RCT) comparing ICIs vs standard therapies in the treatment of unresectable HCC. Data Extraction and Synthesis: The full text of the resulting studies and extracted data were reviewed independently according to PRISMA guidelines. Summary hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were calculated by a random-effects model. The likelihood of ICIs being associated with overall response rate (ORR) and treatment-related adverse events (TRAEs) was expressed by odds ratios (ORs) using a random-effects model. Main Outcomes and Measures: The main outcomes were OS, PFS, ORR, and TRAEs. Results: Of 1836 studies yielded by the search, 3 were retained, totaling 1657 patients (985 treated with ICIs vs 672 receiving standard treatment). Two studies evaluated ICIs as monotherapy, and 1 study investigated the combination of ICIs with bevacizumab. Compared with standard therapies (sorafenib in first-line therapy or placebo in second-line therapy), ICIs were associated with significantly improved OS (HR, 0.75; 95% CI, 0.62-0.92; P = .006), PFS (HR, 0.74; 95% CI, 0.56-0.97; P = .03), and ORR (OR, 2.82; 95% CI 2.02-3.93; P < .001). The probability of grade 3 or 4 TRAEs was lower with ICIs than with sorafenib (OR, 0.44; 95% CI, 0.20-0.96; P = .04). Conclusions and Relevance: This meta-analysis found superior efficacy and safety associated with ICIs compared with standard therapies and highlights the survival benefit associated with the combination of antiangiogenic therapy with ICIs in first-line systemic therapy of unresectable HCC.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Drug-Related Side Effects and Adverse Reactions/epidemiology , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/adverse effects , Liver Neoplasms/drug therapy , Carcinoma, Hepatocellular/mortality , Drug-Related Side Effects and Adverse Reactions/etiology , Humans , Liver Neoplasms/mortality , Progression-Free Survival , Randomized Controlled Trials as Topic , Sorafenib/therapeutic use , Treatment Outcome
11.
Lima; INEN; 3 ago. 2021.
Non-conventional in Spanish | BRISA/RedTESA | ID: biblio-1337728

ABSTRACT

ANTECEDENTES Solicitud presentada por el Comité Farmacoterapéutico del Instituto Nacional de Enfermedades Neoplásicas, en relación con la evaluación y aprobación de Lenvatinib y Sorafenib, en el tratamiento de cáncer diferenciado de tiroides irresecable o metastásico, refractario a tratamiento con yodo radioactivo. ESTRATEGIA DE BÚSQUEDA DE INFORMACIÓN: Pregunta Clínica: En los pacientes con cáncer diferenciado de tiroides irresecable o metastásico, refractario a tratamiento con yodo radioactivo, ¿es eficaz y seguro el tratamiento con inhibidores multiquinasas? Recolección de los Manuscritos a Revisar: Tipos de estudios: La estrategia de búsqueda sistemática de información científica para el desarrollo del presente informe se realizó siguiendo las recomendaciones de la Pirámide jerárquica de la evidencia propuesta por Haynes y se consideró los siguientes estudios: Sumarios y guías de práctica clínica. Revisiones sistemáticas y/o meta-análisis. Ensayos Controlados Aleatorizados (ECA) ● Estudios Observacionales (cohortes, caso y control, descriptivos) No hubo limitaciones acerca de la fecha de publicación o el idioma para ningún estudio. Fuentes de información: De acceso libre. Bases de datos: Pubmed, Cochrane. Fecha de búsqueda: La búsqueda sistemática incluyó a todos los estudios publicados sin límite de antigüedad. Términos de Búsqueda: Considerando la pregunta PICO se construyó dos estrategias de búsqueda, sin restricciones en el idioma ni en periodo de publicación. DISCUSIÓN: Tomando los criterios para un marco de valor de la Health Technology Assessment International (2018)28 para la toma de decisiones y formulación de la recomendación, se describe: La calidad de la evidencia es alta. La evidencia analizada ha consistido en revisiones sistemáticas tanto con meta análisis y de red, los cuales encabezan la pirámide de calidad de evidencia, así como ECA, GPC y ETS de agencias reconocidas. Los ensayos clínicos muestran que lenvatinib y sorafenib son efectivos para retrasar la progresión de la enfermedad, pero hay una tasa de respuesta más alta con lenvatinib y puede retrasar la progresión por más tiempo. Evaluación económica en la región no se tiene, sin embargo, en Reino Unido se realizó una, en la cual, las estimaciones de rentabilidad son más altas de lo que NICE normalmente considera aceptable. Pero los tratamientos aumentan la duración de la vida y no hay otros tratamientos disponibles para la afección. Además, las estimaciones de rentabilidad no capturan los beneficios de que las personas tengan una respuesta al tratamiento, es decir, una mejora de los síntomas. CONCLUSIONES: El cáncer de tiroides es una enfermedad oncológica de buen pronóstico en la mayoría de los casos. Existe un porcentaje de pacientes que desarrollará una progresión recurrencia o enfermedad metastásica refractaria a yodo radioactivo, siendo esta, de mal pronóstico. El tratamiento sistémico para los pacientes con CDT - RR se basa en inhibidores multiquinasas: Sorafenib y Lenvatinib. Sorafenib y Lenvatinib, han demostrado eficacia sobre placebo respecto a la SLP, sin embargo, también se ha demostrado la presencia de EA que han llevado a reducción de dosis y/o interrupción del tratamiento. Nuestro análisis para evaluar el beneficio neto de ambas tecnologías en base a los ECAs fase 3, demuestra una superioridad de Lenvatinib sobre Sorafenib. Las RS analizadas han demostrado la eficacia de ambos IMK versus placebo y una mayor eficacia de Lenvatinib sobre Sorafenib, a pesar de la mayor cantidad de eventos adversos. No se cuenta con evaluaciones económicas en la región, sin embargo, en la EE realizada por la NICE, se concluyó que a pesar de no ser costo - efectiva, al tratarse de una enfermedad rara, ambas drogas deben ser aprobadas para el manejo de pacientes con CDT - RR. Por lo expuesto, la UFETS en consenso con el Comité de ETS, concluye que Sorafenib y Lenvatinib, son alternativas de terapia en pacientes con CDT - RR con una preferencia de uso para Lenvatinib sobre Sorafenib.


Subject(s)
Humans , Thyroid Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Sorafenib/therapeutic use , Iodine Radioisotopes/adverse effects , Cost-Benefit Analysis
14.
Clin Liver Dis ; 24(4): 719-737, 2020 11.
Article in English | MEDLINE | ID: mdl-33012455

ABSTRACT

Sorafenib was the first tyrosine kinase inhibitor (TKI) that showed success in extending survival in patients with advanced hepatocellular carcinoma (HCC). In recent years, additional TKIs have been shown to improve survival and expanded the armamentarium for treating this malignancy. The current landscape includes other classes of drugs, such as immune checkpoint inhibitors and monoclonal antibodies. The challenge is now placed on how to best select, combine, and sequence drugs with the goal of improving efficacy and minimizing toxicities to deliver better outcomes for HCC patients.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Protein-Tyrosine Kinases/antagonists & inhibitors , Anilides/therapeutic use , Humans , Molecular Targeted Therapy , Phenylurea Compounds/therapeutic use , Pyridines/therapeutic use , Quinolines/therapeutic use , Sorafenib/therapeutic use
15.
Future Oncol ; 16(31): 2511-2520, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32783460

ABSTRACT

Aim: To evaluate sorafenib treatment in Latin American patients with unresectable hepatocellular carcinoma in the real-world GIDEON study. Patients & methods: Sorafenib administration, safety and efficacy were analyzed by Child-Pugh status. Results: Of 90 evaluable patients (37% Child-Pugh A, 46% Child-Pugh B and 3% Child-Pugh C at study entry), 97% started sorafenib at 800 mg/day. Patients with Child-Pugh B7 had the longest median treatment duration of sorafenib (33.1 weeks). Sorafenib-related adverse events occurred in 58% of patients with Child-Pugh A (21% grade 3/4) and 46% with Child-Pugh B (7% grade 3/4). Conclusion: Sorafenib had a similar safety profile across patients with Child-Pugh A and B and is a treatment option for both groups.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Sorafenib/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Child , Female , Humans , Latin America/epidemiology , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Male , Middle Aged , Molecular Targeted Therapy , Neoplasm Grading , Neoplasm Staging , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Sorafenib/administration & dosage , Sorafenib/adverse effects , Treatment Outcome , Young Adult
16.
Rev Assoc Med Bras (1992) ; 66(3): 275-283, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32520145

ABSTRACT

OBJECTIVE: Malignant liver tumors are the fourth leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) accounts for 75-85% of these. Most patients are diagnosed at incurable stages. Palliative care is the appropriate treatment course in these circumstances (chemoembolization and sorafenib). There are few national studies on sorafenib. The objective is to evaluate survival predictors of HCC patients treated with sorafenib and evaluate the compliance of its indication in relation to BCLC recommendations. METHODS: A total of 88 patients with an indication of sorafenib from 2010 to 2017 at the ISCMSP were retrospectively analyzed. Univariate and multivariate analyzes were performed in the search for predictors of survival. RESULTS: The mean age was 61.2 years, 70.5% were men, most were classified as Child-Pugh A (69.3%), and BCLC C (94.3%). Cirrhosis was present in 84.6% and portal hypertension in 55.7%. Hepatitis C virus was the most common etiology (40.9%). Sixty-nine (78.4%) patients received the medication, with the average duration of treatment being 9.7 months. The mean overall survival was 16.8 months. Significant differences were observed in the multivariate analysis: ECOG PS (p = 0.024): Child-Pugh (p = 0.013), time of medication use (p <0.001), clinical worsening (p = 0.031) and portal thrombosis (p = 0.010). CONCLUSION: Absence of portal thrombosis, Child-Pugh A, longer time of medication use, ECOG PS 0, and absence of suspension due to clinical worsening were predictors of better overall survival in the study. The drug's indication complies with BCLC guidelines in 94% of patients.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Sorafenib/therapeutic use , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Epidemiologic Methods , Female , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Palliative Care , Treatment Outcome
17.
Cells ; 9(3)2020 03 06.
Article in English | MEDLINE | ID: mdl-32155825

ABSTRACT

Skin melanoma is one of the most aggressive and difficult-to-treat human malignancies, characterized by poor survival rates, thus requiring urgent novel therapeutic approaches. Although metabolic reprogramming has represented so far, a cancer hallmark, accumulating data indicate a high plasticity of cancer cells in modulating cellular metabolism to adapt to a heterogeneous and continuously changing microenvironment, suggesting a novel therapeutic approach for dietary manipulation in cancer therapy. To this aim, we exposed melanoma cells to combined nutrient-restriction/sorafenib. Results indicate that cell death was efficiently induced, with apoptosis representing the prominent feature. In contrast, autophagy was blocked in the final stage by this treatment, similarly to chloroquine, which also enhanced melanoma cell sensitization to combined treatment. Energy stress was evidenced by associated treatment with mitochondrial dysfunction and glycolysis impairment, suggesting metabolic stress determining melanoma cell death. A reduction of tumor growth after cycles of intermittent fasting together with sorafenib treatment was also observed in vivo, reinforcing that the nutrient shortage can potentiate anti-melanoma therapy. Our findings showed that the restriction of nutrients by intermittent fasting potentiates the effects of sorafenib due to the modulation of cellular metabolism, suggesting that it is possible to harness the energy of cancer cells for the treatment of melanoma.


Subject(s)
Antineoplastic Agents/therapeutic use , Cell Death/drug effects , Sorafenib/therapeutic use , Tumor Microenvironment/drug effects , Antineoplastic Agents/pharmacology , Autophagy , Humans , Melanoma/drug therapy , Melanoma/pathology , Nutrients , Sorafenib/pharmacology
18.
Rev. Assoc. Med. Bras. (1992, Impr.) ; Rev. Assoc. Med. Bras. (1992, Impr.);66(3): 275-283, Mar. 2020. tab, graf
Article in English | Sec. Est. Saúde SP, LILACS | ID: biblio-1136210

ABSTRACT

SUMMARY Malignant liver tumors are the fourth leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) accounts for 75-85% of these. Most patients are diagnosed at incurable stages. Palliative care is the appropriate treatment course in these circumstances (chemoembolization and sorafenib). There are few national studies on sorafenib. The objective is to evaluate survival predictors of HCC patients treated with sorafenib and evaluate the compliance of its indication in relation to BCLC recommendations. METHODS A total of 88 patients with an indication of sorafenib from 2010 to 2017 at the ISCMSP were retrospectively analyzed. Univariate and multivariate analyzes were performed in the search for predictors of survival. RESULTS The mean age was 61.2 years, 70.5% were men, most were classified as Child-Pugh A (69.3%), and BCLC C (94.3%). Cirrhosis was present in 84.6% and portal hypertension in 55.7%. Hepatitis C virus was the most common etiology (40.9%). Sixty-nine (78.4%) patients received the medication, with the average duration of treatment being 9.7 months. The mean overall survival was 16.8 months. Significant differences were observed in the multivariate analysis: ECOG PS (p = 0.024): Child-Pugh (p = 0.013), time of medication use (p <0.001), clinical worsening (p = 0.031) and portal thrombosis (p = 0.010). CONCLUSION Absence of portal thrombosis, Child-Pugh A, longer time of medication use, ECOG PS 0, and absence of suspension due to clinical worsening were predictors of better overall survival in the study. The drug's indication complies with BCLC guidelines in 94% of patients.


RESUMO Tumores malignos do fígado são a quarta maior causa de morte por câncer, sendo que o carcinoma hepatocelular (CHC) corresponde a 85-90% desses casos. A maioria dos doentes apresenta-se, ao diagnóstico, sem possibilidade de tratamento curativo, restando apenas as opções paliativas (quimioembolização e sorafenibe). Há poucos estudos nacionais acerca do sorafenibe. OBJETIVO Avaliar fatores preditivos de sobrevida em pacientes com CHC que tiveram indicação de tratamento com sorafenibe na Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP) e avaliação da conformidade da indicação da medicação em relação às recomendações do BCLC. MÉTODOS Foram analisados retrospectivamente os dados de 88 pacientes que tiveram indicação de tratamento com sorafenibe no período de 2010 a 2017 na ISCMSP. Análises univariada e multivariada foram realizadas na busca de preditores de sobrevida global nos pacientes que receberam a medicação. RESULTADOS Idade média de 61,2 anos, sendo 70,5% homens. A maioria (69,3%) foi classificada como Child Pugh A e BCLC C (94,3%). A cirrose esteve presente em 84,6% e a hipertensão portal em 55,7% desses. O vírus da hepatite C foi a etiologia mais comum (40,9%) do CHC. Sessenta e nove (78,4%) pacientes receberam a medicação, sendo o tempo médio de duração do tratamento 9,7 meses e a sobrevida global média, 16,8 meses. Diferenças significativas foram observadas na análise multivariada: Ecog PS (p=0,024), CP (p=0,013), tempo de uso de medicação (p<0,001), suspensão por piora clínica (p=0,031) e trombose portal (p=0,010). CONCLUSÃO Ausência de trombose portal, Child Pugh A, Ecog PS 0, tempo maior de uso de medicação e ausência de suspensão por piora clínica foram fatores preditores de melhor sobrevida global e a indicação da medicação esteve em conformidade com as orientações do BCLC em 94% dos pacientes.


Subject(s)
Humans , Male , Female , Carcinoma, Hepatocellular/drug therapy , Sorafenib/therapeutic use , Liver Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Palliative Care , Epidemiologic Methods , Treatment Outcome , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Middle Aged , Neoplasm Staging
19.
BMJ Case Rep ; 12(10)2019 Oct 10.
Article in English | MEDLINE | ID: mdl-31604717

ABSTRACT

Hepatocellular carcinoma (HCC) is a terminal, yet preventable, outcome of untreated infection with hepatitis B virus (HBV). HBV is endemic in many areas of Latin America and the Caribbean, including Haiti. Haitians have the highest incidence of liver cancer among Caribbean immigrants. Unfortunately, many of these patients are not screened, despite current guidelines. As HBV is treatable, screening of high-risk populations is crucial to early intervention and prevention of poor outcomes. We highlight the case of a young Haitian male immigrant who presented with unintentional weight loss and epigastric pain and found to have HCC associated with HBV. Despite chemotherapy, the patient died 15 months after diagnosis. Increased awareness of HBV among patients from high-incidence countries may result in early recognition of this disease and reduced morbidity and mortality from devastating complications.


Subject(s)
Carcinoma, Hepatocellular/virology , Hepatitis B, Chronic/complications , Liver Neoplasms/virology , Adult , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/drug therapy , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Diagnosis, Differential , Fatal Outcome , Haiti , Hepatitis B, Chronic/diagnosis , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Male , Mass Screening , Oxaliplatin/therapeutic use , Practice Guidelines as Topic , Sorafenib/therapeutic use , Tomography, X-Ray Computed , Gemcitabine
20.
Blood ; 134(9): 741-745, 2019 08 29.
Article in English | MEDLINE | ID: mdl-31243041

ABSTRACT

The natural history of FLT3-mutated AML is changing after the approval of midostaurin for frontline therapy and gilteritinib for relapsed or refractory patients. Recently reported, positive randomized trials of the drugs gilteritinib, quizartinib, and sorafenib predict even wider use of FLT3 inhibitors going forward. FLT3 inhibitors now emerge as an important, if not indispensable, part of therapy for a large subset of high-risk patients.


Subject(s)
Antineoplastic Agents/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Protein Kinase Inhibitors/therapeutic use , fms-Like Tyrosine Kinase 3/antagonists & inhibitors , Aniline Compounds/pharmacology , Aniline Compounds/therapeutic use , Animals , Antineoplastic Agents/pharmacology , Benzothiazoles/pharmacology , Benzothiazoles/therapeutic use , Clinical Trials as Topic , Humans , Phenylurea Compounds/pharmacology , Phenylurea Compounds/therapeutic use , Protein Kinase Inhibitors/pharmacology , Pyrazines/pharmacology , Pyrazines/therapeutic use , Sorafenib/pharmacology , Sorafenib/therapeutic use , Staurosporine/analogs & derivatives , Staurosporine/pharmacology , Staurosporine/therapeutic use
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