RESUMO
OBJECTIVE: The clinical efficacy and safety of sorafenib in patients with advanced liver cancer (ALC) were evaluated based on transarterial chemoembolization (TACE). METHODS: 92 patients with ALC admitted to our hospital from May 2020 to August 2022 were randomly rolled into a control (Ctrl) group and an observation (Obs) group, with 46 patients in each. Patients in the Ctrl group received TACE treatment, while those in the Obs group received sorafenib molecular targeted therapy (SMTT) on the basis of the treatment strategy in the Ctrl group (400 mg/dose, twice daily, followed by a 4-week follow-up observation). Clinical efficacy, disease control rate (DCR), survival time (ST), immune indicators (CD3+, CD4+, CD4+/CD8+), and adverse reactions (ARs) (including mild fatigue, liver pain, hand-foot syndrome (HFS), diarrhea, and fever) were compared for patients in different groups after different treatments. RESULTS: the DCR in the Obs group (90%) was greatly higher to that in the Ctrl group (78%), showing an obvious difference (P < 0.05). The median ST in the Obs group was obviously longer and the median disease progression time (DPT) was shorter, exhibiting great differences with those in the Ctrl group (P < 0.05). Moreover, no great difference was observed in laboratory indicators between patients in various groups (P > 0.05). After treatment, the Obs group exhibited better levels in all indicators. Furthermore, the incidence of ARs in the Obs group was lower and exhibited a sharp difference with that in the Ctrl group (P < 0.05). CONCLUSION: SMTT had demonstrated good efficacy in patients with ALC, improving the DCR, enhancing the immune response of the body, and reducing the incidence of ARs, thereby promoting the disease outcome. Therefore, it was a treatment method worthy of promotion and application.
Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Antineoplásicos/efeitos adversos , Quimioembolização Terapêutica/métodos , Niacinamida/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Resultado do Tratamento , Terapia CombinadaRESUMO
BACKGROUND: Non-immunosuppressed patients with a history of multiple non-melanoma skin cancers (NMSCs) taking oral nicotinamide supplementation experienced a 23% decrease in annual NMSC risk in a randomized clinical trial. Patient preferences for risks and costs associated with nicotinamide are unknown. OBJECTIVES: To understand how patients prioritize NMSC reduction, infection risk, and cost. METHODS: A sample of adults with history of ≥2 NMSC within the past five years undergoing Mohs procedure completed a discrete-choice experiment comprising two hypothetical treatments-characterized by varying reductions in NMSC incidence, increased severe infection risk, and cost-and no treatment. The data were analyzed with random-parameters logit models. RESULTS: A total of 203 subjects (mean age 71.5 years, 65.5% males) participated. For a 23% annual reduction in NMSC incidence, a 26% [95% CI: 8%-45%] annual increase in severe infection risk and $8 [95% CI: $2-14] monthly cost was acceptable. Outcomes across analyzed subgroups (before vs. during COVID pandemic, site of interview, less vs. more prior NMSCs) were similar. CONCLUSIONS: Patients were unwilling to accept high severe infection risks to obtain the reduction in NMSC incidence observed in a nicotinamide trial, suggesting that routinely recommending nicotinamide may run counter to some patients' preferences.
Assuntos
COVID-19 , Neoplasias Cutâneas , Adulto , Masculino , Humanos , Idoso , Feminino , Modelos Logísticos , Niacinamida/efeitos adversos , Pandemias , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/prevenção & controleAssuntos
Creatinina/metabolismo , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Niacinamida/análogos & derivados , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Transportador 2 de Cátion Orgânico/metabolismo , Eliminação Renal , Acidose Láctica/induzido quimicamente , Antiarrítmicos/efeitos adversos , Antibacterianos/efeitos adversos , Antivirais/efeitos adversos , Área Sob a Curva , Biomarcadores/metabolismo , Interações Medicamentosas , Células HEK293 , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Humanos , Técnicas In Vitro , Niacinamida/efeitos adversos , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Transportador 2 de Cátion Orgânico/antagonistas & inibidores , Inibidores da Bomba de Prótons/efeitos adversosRESUMO
Nicotinamide (NAM) at doses far above those recommended for vitamins is suggested to be effective against a wide spectrum of diseases and conditions, including neurological dysfunctions, depression and other psychological disorders, and inflammatory diseases. Recent increases in public awareness on possible pro-longevity effects of nicotinamide adenine dinucleotide (NAD+) precursors have caused further growth of NAM consumption not only for clinical treatments, but also as a dietary supplement, raising concerns on the safety of its long-term use. However, possible adverse effects and their mechanisms are poorly understood. High-level NAM administration can exert negative effects through multiple routes. For example, NAM by itself inhibits poly(ADP-ribose) polymerases (PARPs), which protect genome integrity. Elevation of the NAD+ pool alters cellular energy metabolism. Meanwhile, high-level NAM alters cellular methyl metabolism and affects methylation of DNA and proteins, leading to changes in cellular transcriptome and proteome. Also, methyl metabolites of NAM, namely methylnicotinamide, are predicted to play roles in certain diseases and conditions. In this review, a collective literature search was performed to provide a comprehensive list of possible adverse effects of NAM and to provide understanding of their underlying mechanisms and assessment of the raised safety concerns. Our review assures safety in current usage level of NAM, but also finds potential risks for epigenetic alterations associated with chronic use of NAM at high doses. It also suggests directions of the future studies to ensure safer application of NAM.
Assuntos
Niacinamida/efeitos adversos , Complexo Vitamínico B/efeitos adversos , Animais , Metilação de DNA , Metabolismo Energético , Humanos , Niacinamida/administração & dosagem , Niacinamida/metabolismo , Estresse Oxidativo , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/metabolismoRESUMO
To investigate the dietary exposure risk of flonicamid application on Lonicerae Japonicae Flos and the effect of flonicamid on constituents of Lonicerae Japonicae Flos, field experiments were conducted in Fengqiu, Henan province, and flonicamid residue in samples collected was detected by gas chromatography equipped with electron capture detector (GC-ECD). And chlorogenic acid and luteoloside were determined by HPLC. Dietary exposure risk assessment was conducted through comparing the estimated daily intake (EDI) which was calculated by using the consumed residual level along with the acceptable daily intake (ADI). The effect of flonicamid on chlorogenic acid and luteoloside were obtained by ANOVA statistical analysis and least significant difference (LSD)-t test. The results showed that the terminal-residue contents of flonicamid were under 1.6 mg kg-1. And risk quotient ranged from 0.0011 to 0.0028, indicating the long-term exposure to flonicamid residual through consumption of Lonicerae Japonicae Flos in consumers was relatively low. Flonicamid could suppress the generation of luteoloside, so it was not advised to be used in L. japonica flowering phase. The study aims at providing the useful suggestion on the reasonable flonicamid usage and the reference for the establishment of maximum residue limits (MRLs) of flonicamid in Lonicerae Japonicae Flos.
Assuntos
Niacinamida/análogos & derivados , Extratos Vegetais/química , Exposição Dietética , Lonicera , Niacinamida/efeitos adversos , Niacinamida/análise , Medição de RiscoRESUMO
BACKGROUND: This study aimed to investigate the safety of sorafenib for the treatment of unresectable hepatocellular carcinoma in Chinese patients. METHODS: A subgroup of 345 Chinese patients from the international database of the Global Investigation of therapeutic DEcisions in hepatocellular carcinoma and Of its treatment with sorafeNib (GIDEON) study was included in this analysis. Safety assessment measures were adverse events (AEs) and serious adverse events (SAEs) graded using the National Cancer Institute Common Terminology Criteria version 3.0. RESULTS: Of 331 evaluable patients, 98% started sorafenib at 800 mg/day. The median treatment duration was 22 weeks (range, 0.1-116 weeks), and median overall survival (OS) was 322 days (10.7 months). Approximately 50% of patients had at least one adverse event, and 6% had grade 3-4 adverse events. Drug-related adverse events were experienced by 29% of patients, and 3.6% had grade 3-4 drug-related adverse events. Overall, 23% of patients (n = 77) experienced serious adverse events, among which only 1 event was drug-related (0.3%). No differences in overall adverse events, serious adverse events, and deaths were observed between Child-Pugh A and Child-Pugh B patients. The most frequent drug-related adverse events were dermatological/skin (24%), hand-foot skin reaction (20%), gastrointestinal (11%), and diarrhea (11%). The majority of adverse events occurred within 30 days of beginning sorafenib. CONCLUSION: Sorafenib has satisfactory efficacy and safety in Chinese Child-Pugh A and B patients with unresectable HCC using the recommended dosage of 800 mg/day, and the safety of sorafenib is not affected by liver function. Prophylaxis for gastrointestinal adverse events may help to decrease dose interruptions or discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov ; Identifier: NCT00812175. Date of registration: December 19, 2008.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/patologia , Masculino , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Estudos Retrospectivos , Segurança , Sorafenibe , Resultado do TratamentoRESUMO
BACKGROUND: Lenvatinib (Lenvima®) and sorafenib (Nexavar®) are the two most recently Food and Drug Administration-approved drugs for treating radioiodine-refractory differentiated thyroid cancer (RR-DTC). Both demonstrated superior progression-free survival over placebo in their respective Phase III clinical trials. This study compared the cost-effectiveness of the two treatments with placebo from a limited societal perspective. METHODS: A Markov model was developed to estimate the costs and health benefits for treatment of RR-DTC. The probabilities and survival rates were obtained from two Phase III trials: the SELECT trial comparing lenvatinib to placebo, and the DECISION trial comparing sorafenib to placebo. A bimonthly cycle length and half-cycle correction were used for a lifetime time horizon. Medical costs and utility data were obtained from RedBook, Healthcare Cost and Utilization Project, and the published literature. All costs were adjusted to US$2015, discounted at 3% annually. Then second-order Monte Carlo simulation with distributions was conducted to obtain the acceptability curve to address the uncertainty around model inputs. RESULTS: In the base case, lenvatinib was the most cost-effective treatment compared to sorafenib (incremental cost-effectiveness ratio [ICER] = $25,275/quality-adjusted life year [QALY]) and placebo (ICER = $40,869). Sorafenib is also cost-effective compared to placebo (ICER = $64,067/QALY). The treatment decisions were found to be sensitive to the treatment costs and the health utility associated with lenvatinib and its side effects. The acceptability curve showed lenvatinib optimal 80% of time at WTP of $100,000/QALY. CONCLUSIONS: This study suggests that lenvatinib is the optimally cost-effective treatment for RR-DTC, although both lenvatinib and sorafenib are cost-effective compared to placebo.
Assuntos
Antineoplásicos/uso terapêutico , Modelos Econômicos , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Qualidade de Vida , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/economia , Diferenciação Celular , Ensaios Clínicos Fase III como Assunto , Ensaios Clínicos Controlados como Assunto , Análise Custo-Benefício , Custos de Medicamentos , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Método de Monte Carlo , Gradação de Tumores , Niacinamida/efeitos adversos , Niacinamida/economia , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/economia , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/economia , Quinolinas/efeitos adversos , Quinolinas/economia , Sorafenibe , Análise de Sobrevida , Neoplasias da Glândula Tireoide/economia , Neoplasias da Glândula Tireoide/patologia , Carga Tumoral/efeitos dos fármacos , Estados UnidosRESUMO
BACKGROUND: Phase III trials show sorafenib improves survival in advanced hepatocellular carcinoma (HCC). Because of narrow trial eligibility, results may not be generalizable to a broader HCC population. We sought to evaluate the effectiveness of initial sorafenib versus no treatment among Medicare beneficiaries with advanced HCC. MATERIALS AND METHODS: Patients with advanced HCC diagnosed from 2008 to 2011 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Eligible patients received initial sorafenib or no therapy and were covered by Medicare parts A, B, and D. Sorafenib use and outcomes were described in this population. Using a propensity score (PS)-matched sample, we compared the effectiveness of sorafenib versus no treatment by Cox proportional hazards and binomial regression, using a landmark requiring all patients to survive ≥60 days after diagnosis. RESULTS: Of 1,532 patients, 27% received initial sorafenib. Median duration of sorafenib use was 60 days (interquartile range [IQR], 30-107 days), and median survival from first prescription was 3 months (IQR, 1-8 months). In the PS-matched cohort, median survival was 3 months from the 60-day landmark in sorafenib-treated (n = 223) and 2 months in untreated (n = 223) patients (adjusted hazard ratio, 0.95 [95% confidence interval (CI), 0.78-1.16]). Sorafenib was associated with a nonsignificant reduction in mortality at 3 months (44% versus 51%; adjusted risk ratio, 0.88 [95% CI, 0.72-1.07]), but no reduction thereafter. CONCLUSION: Survival after sorafenib initiation in newly diagnosed Medicare beneficiaries with HCC is exceptionally short, suggesting trial results are not generalizable to all HCC patients. The downsides of sorafenib use-high drug-related symptom burden and high drug cost-must be considered in light of this minimal benefit. IMPLICATIONS FOR PRACTICE: The findings of a median survival of only 3 months in Medicare beneficiaries with HCC prescribed sorafenib as first-line therapy highlight the questionable value of sorafenib in this population. Patients should be cautioned that outside of the narrow confines of randomized trials, their life expectancy may be very short, and any benefit of sorafenib is likely to be quite small. Given that sorafenib causes considerable adverse effects and offers no symptom palliation, supportive care should be discussed as a reasonable alternative to sorafenib, particularly for patients who have a poor performance status or advanced cirrhosis.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/patologia , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Custos de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Sorafenibe , Resultado do TratamentoRESUMO
Angiogenesis inhibition is a major antitumor strategy that has emerged during the last decade. Oral tyrosine kinase inhibitors (TKI) targeting the VEGF receptor, including sunitinib, sorafenib, axitinib, regorafenib, pazopanib, and vandetanib reduce tumor growth and metastasis. These agents are approved for the treatment of metastatic diseases in first or second-line. They display a narrow therapeutic index. However, data in the elderly and/or in patients with multiple illnesses remain scarce. This population is classically excluded from clinical trials. The aim of this review is to provide an overview of existing literature regarding antiangiogenic TKI tolerance in the elderly (>70 years old). We also highlight key points of the pre-therapeutic evaluation and summarize the management of common toxicities.
Assuntos
Inibidores da Angiogênese/efeitos adversos , Neovascularização Patológica/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Axitinibe , Fadiga/induzido quimicamente , Humanos , Imidazóis/efeitos adversos , Indazóis/efeitos adversos , Indóis/efeitos adversos , Rim/efeitos dos fármacos , Niacinamida/efeitos adversos , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Piperidinas/efeitos adversos , Piridinas/efeitos adversos , Pirróis/efeitos adversos , Quinazolinas/efeitos adversos , Sorafenibe , SunitinibeRESUMO
BACKGROUND: Untreated advanced hepatocellular carcinoma (HCC) is linked to poor prognosis. While sorafenib is the current recommended treatment for advanced HCC, radioembolisation (RE; also called selective internal radiation therapy or SIRT) with yttrium-90 microspheres has shown efficacy in cohort studies. However, there are no head-to-head trials comparing radiation therapy with yttrium-90 microspheres and sorafenib in advanced HCC. The SARAH trial has been designed to compare the efficacy and safety of sorafenib therapy and RE using yttrium-90 resin microspheres (SIR-Spheres™; Sirtex Medical Limited, North Sydney, Australia) in patients with advanced HCC. Quality of life (QoL) and cost-effectiveness will also be compared between therapies. METHODS/DESIGN: SARAH is a prospective, randomised, controlled, open-label, multicentre trial comparing the efficacy of RE with sorafenib in the treatment of patients with advanced HCC. The trial aims to recruit adults with a life expectancy of >3 months, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1, and: advanced HCC according to the Barcelona criteria (stage C) or recurrent HCC after surgical or thermoablative treatment who are not eligible for surgical resection, liver transplantation or thermal ablation; or two rounds of failed chemoembolisation. Patients will be randomised 1:1 to receive either RE or sorafenib 400 mg twice daily. All patients will be monitored for between 12 and 48 months following start of treatment. The primary endpoint of the SARAH trial is overall survival (OS). Secondary endpoints include: adverse events, progression-free survival at 6 months; tumour response rate; general or liver disease-specific QoL scores; and cost of each treatment strategy. Assuming an increase in median OS of 4 months with RE versus sorafenib therapy, randomising at least 400 patients (200 in each treatment arm) will be sufficient for 80% power and a bilateral alpha risk of 5%; therefore, 440 patients will be enrolled to allow for 10% loss of patients due to ineligibility. DISCUSSION: The SARAH trial is the first randomised head-to-head study to compare RE with sorafenib in advanced HCC, and will establish the potential role of RE in HCC treatment guidelines. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01482442, first received 28 November 2011.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Embolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Projetos de Pesquisa , Radioisótopos de Ítrio/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/economia , Carcinoma Hepatocelular/economia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Protocolos Clínicos , Análise Custo-Benefício , Progressão da Doença , Intervalo Livre de Doença , Custos de Medicamentos , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/economia , França , Humanos , Neoplasias Hepáticas/economia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Microesferas , Niacinamida/efeitos adversos , Niacinamida/economia , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/economia , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/economia , Qualidade de Vida , Sorafenibe , Fatores de Tempo , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversos , Radioisótopos de Ítrio/economiaRESUMO
INTRODUCTION: Sorafenib is a multi-tyrosine kinase inhibitor (TKI). Considerable clinical experience has been accumulated since its first Phase III clinical trial in metastatic renal cancer patients in 2007. The management of its early acute toxicity in fit patients is well known. The management of prolonged treatment becomes the new challenge. AREAS COVERED: Using sorafenib as a key word for PubMed search, we review preclinical and clinical data and discuss the pharmacokinetics and pharmacodynamics of sorafenib, its acute and cumulative toxicities and their consequences for patient management. EXPERT OPINION: The systematic multi-disciplinary risk assessment of cancer patients prior to TKI initiation reduces the risks of acute and late toxicity, especially drug-drug interactions and arterial risks. Sarcopenia is now identified as a major risk of severe toxicity. The very diverse clinical pictures of cumulative toxicity must be known. The monitoring of sorafenib systemic exposure is helpful especially in elderly patients. Moreover, at disease progression, it allows distinguishing between underexposure to sorafenib and truly acquired resistance to the drug. The optimal use of sorafenib should allow improving the reported results of flat-dose. Finally, most of this knowledge could be used for the development and optimal use of the other TKIs.
Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Administração de Caso , Interações Medicamentosas , Humanos , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/farmacocinética , Niacinamida/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/farmacocinética , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacocinética , Medição de Risco , SorafenibeRESUMO
BACKGROUND: Sorafenib, an oral multityrosine kinase inhibitor, has been approved for treatment of unresectable hepatocellular carcinoma (HCC). British Columbia (BC) was the first province in Canada to provide drug coverage for sorafenib. OBJECTIVE: To review the BC experience with sorafenib to assess its effectiveness and tolerance in a 'real-world' clinical setting. METHODS: A retrospective clinic chart review identified 99 patients referred to the BC Cancer Agency from 2008 to 2010 with a diagnosis of HCC who qualified for treatment with sorafenib. RESULTS: Therapy with sorafenib was initiated and continued at a reduced dosage of 400 mg/day in 66 of 99 patients, with 22 patients requiring further dose reduction. Full- and reduced-dose group patients had similar baseline characteristics, except for a higher proportion of female patients (P=0.02) and individuals with alcoholic liver disease (P=0.04) in the full-dose group. The incidence of any grade of adverse effects was higher in the full-dose group (94% versus 77% in the reduced-dose group; P=0.04). Dose reduction rates were significantly higher in the full-dose group, occurring in 66% versus 24% of reduced-dose group patients (P=0.001). The overall survival rates were similar between the two groups: 7.8 months versus 7.1 months in full- versus reduced-dose groups (P=0.14), as were radiological progression rates and alpha-fetoprotein levels. CONCLUSIONS: In a review of 99 patients in a 'real-world' community setting, a sorafenib dose of 400 mg/day was better tolerated and had similar efficacy compared with a sorafenib dose of 800 mg/day with respect to survival and outcomes.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Colúmbia Britânica , Carcinoma Hepatocelular/patologia , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Cobertura do Seguro , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Sorafenibe , Taxa de Sobrevida , Resultado do Tratamento , alfa-Fetoproteínas/metabolismoRESUMO
Sixty patients were randomized to treatment with cytoflavin (n=30) or nootropil (n=30). Patients of the main group received cytoflavin along with standard treatment for correction of hemodynamics. The treatment scheme was as follows: intravenous injections during 10 days, tablets - from 11 to 35 days. The same scheme of treatment was used in the comparison group. The total duration was 35 days. Patients were assessed with NIHSS, the Rankin scale, the Barthel index, MMSE. MRI was used to verify ischemic lesions. The therapeutic efficacy of cytoflavin was significantly higher compared to nootropil in respect to the restoration of neurological functions and self-service abilities as well as to the reduction of cognitive deficit.
Assuntos
Antioxidantes/uso terapêutico , Mononucleotídeo de Flavina/uso terapêutico , Inosina Difosfato/uso terapêutico , Síndrome Metabólica/complicações , Fármacos Neuroprotetores/uso terapêutico , Niacinamida/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Succinatos/uso terapêutico , Administração Intravenosa , Idoso , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Combinação de Medicamentos , Feminino , Mononucleotídeo de Flavina/administração & dosagem , Mononucleotídeo de Flavina/efeitos adversos , Humanos , Inosina Difosfato/administração & dosagem , Inosina Difosfato/efeitos adversos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/administração & dosagem , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Piracetam/administração & dosagem , Piracetam/uso terapêutico , Acidente Vascular Cerebral/complicações , Succinatos/administração & dosagem , Succinatos/efeitos adversos , Resultado do TratamentoRESUMO
AIM: to evaluate treatment compliance and survival of patients receiving oral sorafenib in Indonesia. METHODS: a prospective cohort trial. Unresectable Hepatocelullar carcinoma patients receiving Sorafenib in NexPAP program were recruited between October 2008 and September 2011. A historical cohort from Cipto Mangunkusumo Hospital, between 1998 and 2000 was selected to serve as control group. Patients in the control group received symptomatic treatment. Survival analysis was done by the Kaplan-Meier survival curve analysis and the log-rank test. Median survival difference between the NexPAP and control group was tested using the Cox-regression hazard analysis. RESULTS: There were 48 patients in the NexPAP group and 40 patients in the control group. Treatment compliance was very good; no patient with drew from the study. Sorafenib generally could be tolerated by the patients. The most common adverse events are mild or moderate hand and foot skin reaction and diarrhea. The median survival was 49 weeks in NexPAP group (95% CI 37.9-60.1) vs. 20 weeks in the control group (95% CI 9.0-31.0). Cox-regression analysis showed that sorafenib significantly prolonged overall survival with a hazard ratio (HR) of 0.339 (95% CI: 0.196-0.584). There was no survival difference between patients with Child-Pugh class A and class B in both NexPAP (median 49 vs. 52 weeks; HR 1.1; 95% CI 0.5-2.3; p=0.855) and control groups (27 vs. 20 weeks; HR 1.1; 95% CI 0.5-2.4; p=0.822). CONCLUSION: Sorafenib patient assistant program in unresectable hepatocellular carcinoma ensured compliance treatment and significantly prolonged overall survival over the historical cohort receiving palliative treatment.