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1.
Int J Mol Sci ; 24(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36675198

RESUMO

Sorafenib is currently a targeted agent widely used in the treatment of advanced hepatocellular carcinoma (aHCC). However, to date there is still a lack of a reliable marker capable of predicting sorafenib therapeutic responses. Here, we conducted a genome-wide association study (GWAS) to identify candidate single-nucleotide polymorphism outcome predictors in aHCC patients. A total of 74 real-world sorafenib-treated aHCC patients were enrolled for GWAS and outcome analysis. GWAS showed that rs1010816 (p = 2.2 × 10-7) was associated with sorafenib therapeutic response in aHCC patients. Kaplan-Meier analysis indicated that the "TT" genotype was significantly associated with a favorable therapeutic response but not significantly associated with overall survival (OS). Univariate followed by multivariate Cox proportional hazard analysis showed that ascites, main portal vein thrombosis, lower platelet count, lower total sorafenib doses, higher PALBI score in model A and higher ALBI grade in model B were significantly associated with a shorter OS. Subgroup analysis showed that only in alcoholic aHCC patients treated by sorafenib, rs1010816 "TT" genotype was significantly associated with longer OS (p = 0.021). Sorafenib had a favorable therapeutic outcome in alcoholic aHCC patients carrying rs1010816 "TT" genotype.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Sorafenibe/uso terapêutico , Polimorfismo de Nucleotídeo Único , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Estudo de Associação Genômica Ampla , Antineoplásicos/uso terapêutico , Resultado do Tratamento , Estudos Retrospectivos , Compostos de Fenilureia/uso terapêutico , Niacinamida/uso terapêutico
3.
Eur J Gastroenterol Hepatol ; 35(2): 191-197, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36574310

RESUMO

BACKGROUND AND AIM: An optimal sequential anti-hepatocellular carcinoma (HCC) agent that can be used after failed lenvatinib treatment has not been established. Here, we compared the outcomes of sorafenib and nivolumab as second-line agents after failed lenvatinib treatment in patients with advanced HCC. METHODS: Patients with advanced HCC who had received sorafenib or nivolumab as second-line agents after failed lenvatinib treatment were recruited from two Korean tertiary institutions between November 2018 and June 2020. RESULTS: The median age of the 60 participants (52 treated with sorafenib and eight treated with nivolumab) at baseline was 56.8 years. The demographic, laboratory and tumor variables, as well as lenvatinib treatment duration, were similar between the two groups. The median durations of sorafenib and nivolumab treatment were 1.2 and 2.6 months, respectively ( P = 0.164). Twenty-four (40.0%) patients died during the follow-up period (median, 15.8 months). The median overall survival (OS) of the study population was 5.8 months. The median OS of patients treated with sorafenib was significantly longer than the median OS of patients treated with nivolumab (8.7 vs. 3.0 months; P = 0.046). Sorafenib treatment (vs. nivolumab) was independently associated with a lower risk of mortality (hazard ratio = 0.194; 95% confidence interval, 0.053-0.708; P = 0.013). Worse Eastern Cooperative Oncology Group performance status, larger maximal tumor size, lymph node metastases and higher total bilirubin levels were independently associated with increased mortality risk (all P < 0.05). CONCLUSIONS: Lenvatinib-sorafenib sequential treatment resulted in significantly better survival did than lenvatinib-nivolumab sequential treatment in patients with advanced HCC. Larger studies are needed to validate our results.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Pessoa de Meia-Idade , Sorafenibe/efeitos adversos , Carcinoma Hepatocelular/patologia , Nivolumabe/efeitos adversos , Antineoplásicos/efeitos adversos , Neoplasias Hepáticas/patologia , Compostos de Fenilureia/efeitos adversos , Falha de Tratamento
4.
Intern Med ; 61(8): 1211-1217, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-34544944

RESUMO

Lenvatinib is a multi-targeted tyrosine kinase inhibitor available for the treatment of unresectable hepatocellular carcinoma (HCC). We herein report an 84-year-old-man with interstitial pneumonia caused by lenvatinib. Four months after the start of lenvatinib administration for HCC, chest computed tomography revealed bilateral ground-glass opacity. However, he continued to take lenvatinib for four more months until he complained of dyspnea on exertion. This is a case of lenvatinib-induced interstitial pneumonia that progressed relatively slowly with a long asymptomatic period despite the appearance of pneumonia on image findings.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Doenças Pulmonares Intersticiais , Quinolinas , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Masculino , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos
5.
BMC Geriatr ; 22(1): 987, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36539696

RESUMO

OBJECTIVE: This is the first clinical study that wants to investigate the treatment patterns, clinical outcomes, and prognostic factors of regorafenib plus PD-1 inhibitors therapy in Chinese elderly patients with advanced colorectal cancer. METHODS: A cohort of metastatic colorectal cancer patients 60 years or older who received treatment with regorafenib combined with PD-1 inhibitors was included in our analysis. The endpoints included overall survival (OS), progression-free survival (PFS), and prognostic factors. RESULTS: In total, 24 patients were enrolled with the median age of 68 years, and 62.5% were female. The median OS and PFS were 15.03 months (95% CI 7.0-23.0) and 4.0 months (95% CI 1.8-6.2), respectively. The objective response rate was 8.3%, and the disease control rate was 70.8%. Patients previously treated with regorafenib had a longer median PFS than those without (6.3 versus 2.8 months). In terms of final daily doses, it showed a trend toward better PFS (median PFS was 10.0 months) in high-dose group (daily dose above 80 mg of regorafenib) compared to low-dose group (daily dose no more than 80 mg of regorafenib) (median PFS was 3.5 months). CONCLUSIONS: This real-world evidence confirms that Chinese elderly patients with advanced colorectal cancer may benefit from the treatment of regorafenib combined with PD-1 inhibitors, similarly with this combination therapy strategies in all age patients.


Assuntos
Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Humanos , Feminino , Idoso , Masculino , Inibidores de Checkpoint Imunológico/uso terapêutico , Piridinas/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/efeitos adversos
6.
J Cancer Res Ther ; 18(Supplement): S367-S373, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36510990

RESUMO

Background: Colorectal cancer is the ninth leading cause of death in Spain. The latest therapeutic developments in the advanced stages of this disease are the oral drugs trifluridine/tipiracil and regorafenib. Objective: Results of clinical trials (CTs) are not in real conditions and therefore, we want to study the effectiveness and the safety profile in the usual clinical practice and compare it with the bibliography. Materials and Methods: A retrospective and unicentric study was carried out in a health area of 500,000 inhabitants. Patients who started treatment with regorafenib and/or trifluridine/tipiracil were included from the date of marketing until June 2019. Patient-related variables, pathology, effectiveness, and treatment toxicity were collected. The statistical analysis was carried out with the PSPP program. Results: Fifty-four patients were analyzed. Men accounted for 59.3% of patients. Regorafenib was the treatment for 22.2% of patients and 77.8% received trifluridine/tipiracil. The reason for the drug's suspension was the disease progression in 85.2% of patients. No patient had a full response and 3.2% achieved partial response. The median progression-free survival time in treatments with regorafenib was 2.5 months (95% confidence interval [CI]: 0.0-5.4) and the overall survival time was 3.1 months (95% CI: 0.0-6.7), while in treatments with trifluridine/tipiracil, these data were, respectively, 2.8 (95% CI: 2.5-3.2) and 5.7 months (95% CI: 3.8-7.6). Side effects occurred in 91.7% of patients treated with regorafenib and in 100% of treated with trifluridine/tipiracil. Hematological adverse reactions were, on average, 0.4 ± 0.5/patient with regorafenib and 1.5 ± 0.9 with trifluridine/tipiracil. General (77.8%) and gastrointestinal disorders (50%) were common with both drugs. Conclusions: The effectiveness results of standard clinical practice are lower than those described in CTs and in the literature. The toxicity profile does reproduce what is described in the bibliography.


Assuntos
Neoplasias Colorretais , Uracila , Masculino , Humanos , Estudos Retrospectivos , Uracila/efeitos adversos , Neoplasias Colorretais/patologia , Trifluridina/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Combinação de Medicamentos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
7.
Oncology (Williston Park) ; 36(12): 732-738, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36548097

RESUMO

OBJECTIVES: To assess the effectiveness and toxicity of regorafenib in patients with metastatic colorectal cancer (mCRC) in routine clinical practice, as well as predictive factors of effectiveness. METHODS: This was a retrospective multicenter study in patients with mCRC who received regorafenib from November 2013 to May 2020. Effectiveness was evaluated by overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method. Cox regression was performed to determine survival predictors. RESULTS: Ninety patients were enrolled (median age, 64.3 years). Fifty-two patients (57.8%) were male, and 57 (63.3%) had an ECOG performance status (PS) of 0 to 1. Median follow-up was 2.80 months. Median OS was 8.03 months (95% CI, 5.90-10.17), and median PFS was 2.90 months (95% CI, 2.59-3.21). Eighty-eight patients (97.8%) experienced drug-related adverse events. The most frequent were fatigue in 66 patients (73.3%), followed by palmar-plantar erythrodysesthesia in 40 (44.4%). Low liver tumor burden score (LTBS) and good ECOG PS were independent OS predictive factors. CONCLUSIONS: Patients taking regorafenib had OS and PFS rates similar to those reported in previous randomized trials; the agent had a poor toxicity profile. We identified low LTBS and good ECOG PS as possible predictive factors of better OS, useful in selecting patients with mCRC who might benefit from regorafenib.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Retais , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Neoplasias Colorretais/patologia , Dados de Saúde Coletados Rotineiramente , Compostos de Fenilureia/efeitos adversos , Neoplasias Hepáticas/secundário
8.
Front Immunol ; 13: 1016736, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505445

RESUMO

Background: Conversion therapy is feasible in patients with oncologically unresectable hepatocellular carcinoma (HCC). However, it is challenging to prospectively identify patients who are more likely to achieve successful conversion before initiating systemic therapy, either alone or combined with locoregional therapy. Methods: Criteria for identifying potentially resectable patients with initially oncologically unresectable HCC before treatment with lenvatinib plus an anti-PD-1 antibody were proposed based on real-world evidence. Multivariate Firth logistic regression was used to validate the proposed criteria in a retrospective cohort of consecutive patients with advanced HCC, who received combination therapy with lenvatinib plus an anti-PD-1 antibody between September 2018 and September 2021. Results: The proposed criteria were as follows: (1) Eastern Cooperative Oncology Group performance status of 0 or 1; (2) Child-Pugh class A; (3) intrahepatic tumors confined to one lobe (left, right, or middle lobe), or present in one lobe alongside a single tumor with diameter ≤5 cm or up to three tumors each with diameter ≤3 cm in the remaining lobes, with R0 resection achievable by hemihepatectomy, alone or combined with locoregional therapy to the remaining lobes during surgery; and (4) no portal vein tumor thrombus involving the contralateral liver lobe or reaching the superior mesenteric vein, no hepatic vein tumor thrombus involving more than two major hepatic vein branches on the tumor side, and no tumor thrombus of the inferior vena cava reaching the atrium. Firth logistic regression confirmed the criteria were an independent predictor of surgery following conversion therapy with lenvatinib plus an anti-PD-1 antibody. Conclusions: This study proposed and validated criteria for identifying patients with initially oncologically unresectable HCC who are potentially resectable when treated with combination therapy with lenvatinib plus an anti-PD-1 antibody. The proposed criteria could help standardize conversion therapy studies in advanced HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico
9.
Gan To Kagaku Ryoho ; 49(12): 1365-1367, 2022 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-36539251

RESUMO

A 57-year-old man was treated with lenvatinib for unresectable hepatocellular carcinoma(HCC). Thereafter, the tumor marker levels decreased, and the tumor became resectable. The patient underwent portal vein embolization followed by laparoscopic extended left lobectomy. The patient's postoperative course was uneventful, and the tumor marker levels remained within the normal range. No recurrence was observed 3 months after surgery. In recent years, the use of systemic chemotherapy with drugs, such as lenvatinib, followed by conversion surgery has been reported in some cases of unresectable HCC. The present case reports successful conversion surgery following lenvatinib treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Quinolinas , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Biomarcadores Tumorais
10.
Int J Mol Sci ; 23(24)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36555845

RESUMO

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The AKT pathway is often activated in HCC cases, and a longer exposure to tyrosine kinase inhibitors such as sorafenib may lead to over-activation of the AKT pathway, leading to HCC resistance. Here, we studied the efficacy of a new generation of allosteric AKT inhibitor, vevorisertib, alone or in combination with sorafenib. To identify specific adverse effects related to the background of cirrhosis, we used a diethylnitrosamine (DEN)-induced cirrhotic rat model. Vevorisertib was tested in vitro on Hep3B, HepG2, HuH7 and PLC/PRF cell lines. Rats were treated weekly with intra-peritoneal injections of DEN for 14 weeks to obtain cirrhosis with fully developed HCC. After that, rats were randomized into four groups (n = 7/group): control, sorafenib, vevorisertib and the combination of vevorisertib + sorafenib, and treated for 6 weeks. Tumor progression was followed by MRI. We demonstrated that the vevorisertib is a highly potent treatment, blocking the phosphorylation of AKT. The tumor progression in the rat liver was significantly reduced by treatment with vevorisertib + sorafenib (49.4%) compared to the control group (158.8%, p < 0.0001). Tumor size, tumor number and tumor cell proliferation were significantly reduced in both the vevorisertib group and vevorisertib + sorafenib groups compared to the control group. Sirius red staining showed an improvement in liver fibrosis by vevorisertib and the combination treatment. Moreover, vevorisertib + sorafenib treatment was associated with a normalization in the liver vasculature. Altogether, vevorisertib as a single agent and its combination with sorafenib exerted a strong suppression of tumor progression and improved liver fibrosis. Thus, results provide a rationale for testing vevorisertib in clinical settings and confirm the importance of targeting AKT in HCC.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Ratos , Animais , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Hepáticas/metabolismo , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proliferação de Células , Cirrose Hepática/tratamento farmacológico
11.
J Chromatogr A ; 1685: 463621, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36334568

RESUMO

Three aryl ketones-derived porous organic polymers (ATP-POPM, ATP-POPP and ATP-POPO) were fabricated through the aldol condensation reaction of acetylated triphenylsilane precursor (ATP) with different aromatic aldehydes for the first time. The ATP-POPM exhibited superior extraction capacity toward phenylurea herbicides (PUHs). A sensitive method for the simultaneous determination of six PUHs in water, tea drink and mushroom samples was developed with ATP-POPM as solid phase extraction adsorbent prior to high performance liquid chromatography ultraviolet detection. Under the optimized conditions, the linear response of PUHs was 0.09-80.0 ng mL-1 for water, 0.18-100.0 ng mL-1 for tea drinks and 4.50-200.0 ng g -1 for mushroom samples. The detection limits (S/N=3) of the method were 0.03-0.10 ng mL-1, 0.06-0.18 ng mL-1, 1.50-4.50 ng g -1 for water, tea drink and mushroom, respectively. The method recoveries for spiked samples were in the range of 80.7%-116.0%, with relative standard deviations less than 10.3%. The results proved that the established method was sensitive and suitable to detect PUHs with acceptable accuracy and precision. This work provided a powerful tool to synthesize promising adsorbent by aldol condensation reaction for detecting six PUHs simultaneously in real samples.


Assuntos
Agaricales , Herbicidas , Herbicidas/análise , Polímeros/química , Água/química , Porosidade , Cetonas/análise , Compostos de Fenilureia/análise , Extração em Fase Sólida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Chá/química , Trifosfato de Adenosina
12.
Eur J Cancer ; 177: 154-163, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36335783

RESUMO

PURPOSE: The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm. RESULTS: There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: population for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 patients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C. CONCLUSIONS: The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher numerical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles. GOV IDENTIFIER: NCT02835924.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Compostos de Fenilureia , Piridinas , Neoplasias Colorretais/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico
13.
J Neurooncol ; 160(2): 389-402, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36309895

RESUMO

PURPOSE: In the phase 2 REGOMA trial, regorafenib improved overall survival, as compared with lomustine, in glioblastoma (GBM) patients at first progression after chemoradiation. Recently, some real-life trials showed similar impact on survival but a higher rate of adverse events than in REGOMA, thus raising concerns over tolerability. The aim of this study was to assess the efficacy and tolerability of a lower intensity regorafenib regimen. PATIENTS AND METHODS: Regorafenib daily dose was gradually increased from 80 to 160 mg across the first 2 cycles. Progression-free survival (PFS) and overall survival (OS) were defined as time from regorafenib initiation and disease progression or death. RESULTS: Sixty-six GBM patients were included. Median age was 60.0 years. Median PFS and OS following regorafenib were 2.7 and 7.1 months, respectively. Best RANO response to regorafenib were partial response (PR) in 10 (15.1%), stable disease in 17 (25.8%), and progressive disease in 39 (59.1%) patients. Forty-six (69.7%) patients presented adverse events of any grade, and 21 (31.8%) grade 3-4 toxicity. In a multivariable analysis, higher age and absence of MGMTp methylation were significantly associated with poorer disease control after regorafenib. CONCLUSIONS: Our study is the largest observational real-life study on the use of regorafenib. Our lower intensity regimen proved as effective as the standard 160 mg daily schedule (mPFS and mOS being 2.7 vs 2.0 months and 7.1 vs 7.4 months in our study vs REGOMA, respectively). Moreover, we observed a higher rate of PRs as compared with REGOMA (15.0% vs 3.0%).


Assuntos
Glioblastoma , Humanos , Pessoa de Meia-Idade , Glioblastoma/tratamento farmacológico , Redução da Medicação , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/induzido quimicamente , Compostos de Fenilureia/efeitos adversos
14.
Cancer Med ; 11 Suppl 1: 5-9, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36202603

RESUMO

Lenvatinib is one the most active drugs in radioiodine-refractory differentiated thyroid cancer (RR-DTC) such that it has become an important therapeutic tool in tumor control and survival. Renal and hepatic impairments are common comorbidities in cancer patients. Treating these patients is a challenge that requires careful consideration. As a first approach to patients with RR-DTC and renal or hepatic impairment, Summary of Product Characteristics recommendations for lenvatinib use and dose adjustments should be strictly followed. Close clinical and blood monitoring is the gold standard approach to optimizing lenvatinib's use during the whole course of treatment.


Assuntos
Adenocarcinoma , Antineoplásicos , Neoplasias da Glândula Tireoide , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/efeitos adversos , Humanos , Radioisótopos do Iodo/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia
15.
Cancer Med ; 11 Suppl 1: 3-4, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36202604

RESUMO

Thyroid cancer is the most frequent endocrine tumor. In locally advanced or metastatic disease there are only two types of treatment available: radioactive iodine (RAI) while the disease is RAI-sensitive and multikinase inhibitors, lenvatinib and sorafenib, when the disease becomes RAI-refractory. The objective of this publication is to review the current knowledge on the use of targeted therapy and the specific practical considerations concerning lenvatinib in the treatment of patients with differentiated thyroid cancer under special circumstances.


Assuntos
Antineoplásicos , Neoplasias da Glândula Tireoide , Antineoplásicos/efeitos adversos , Humanos , Radioisótopos do Iodo/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas , Sorafenibe/uso terapêutico , Neoplasias da Glândula Tireoide/patologia
16.
Cancer Med ; 11 Suppl 1: 17-25, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36202605

RESUMO

Antiangiogenic tyrosine kinase inhibitors are the treatment of choice in radioiodine refractory-differentiated thyroid cancer (RR-DTC). Nevertheless, these therapies present class toxicities that may impact their feasibility and patient's quality of life. Their mechanism of action explains the high prevalence of hypertension associated with their use, which reaches 68% with lenvatinib. Moreover, up to 85% of patients treated in the SELECT clinical trial were receiving baseline antihypertensive treatment. These data support the need for prevention, detection, and early management of hypertension. Prevention can be accomplished by controlling cardiovascular risk factors (hypertension, diabetes, obesity, and dyslipidemia) and those associated with lifestyle (smoking, harmful alcohol consumption, and physical inactivity) and electrolyte disorders. It is necessary to achieve stabilization of cardiovascular diseases. Detection involves baseline measurement and monitoring of blood pressure and cardiac function. Treatment requires optimization of baseline blood pressure and early initiation of antihypertensive agents.


Assuntos
Adenocarcinoma , Antineoplásicos , Doenças Cardiovasculares , Hipertensão , Neoplasias da Glândula Tireoide , Adenocarcinoma/tratamento farmacológico , Anti-Hipertensivos/efeitos adversos , Antineoplásicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Eletrólitos/uso terapêutico , Fatores de Risco de Doenças Cardíacas , Humanos , Hipertensão/induzido quimicamente , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Radioisótopos do Iodo/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Qualidade de Vida , Quinolinas , Fatores de Risco , Neoplasias da Glândula Tireoide/tratamento farmacológico
17.
Cancer Med ; 11 Suppl 1: 47-53, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36202606

RESUMO

Thyroid cancer is the most frequent endocrine tumor. However, in locally advanced or metastatic disease we have only two types of treatment at our disposal: radioactive iodine (RAI) when the disease is RAI-sensitive and multikinase inhibitors (MKIs), lenvatinib and sorafenib, when the disease becomes RAI-refractory (RR). This review revisits the published data on the potential combination of MKIs/lenvatinib with RAI in RR-differentiated thyroid cancer and evaluates some special situations where this combination may be of particular interest. The combination of MKIs/lenvatinib with RAI could, at least hypothetically, improve the efficacy seen in both treatments alone via a synergistic effect and with a lower rate of toxicity rates. Early preclinical data support this notion, while its generalized use awaits the results of ongoing clinical trials.


Assuntos
Adenocarcinoma , Antineoplásicos , Neoplasias da Glândula Tireoide , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/efeitos adversos , Humanos , Radioisótopos do Iodo/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas , Sorafenibe/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia
18.
Cancer Med ; 11 Suppl 1: 26-32, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36202607

RESUMO

This review focuses on patients with differentiated thyroid carcinoma (DTC) associated with multiple primary malignant neoplasm (MPMN) treated by multikinase inhibitors (MKIs) as systemic treatment for advanced disease. Despite the increasing frequency of MPMNs (many at an advanced stage) and the usefulness of MKIs for multiple metastatic cancers, published data on the management of MPMN and MKI therapies in this scenario are scarce. There are infrequent descriptions of patients with advanced MPMN treated with MKIs, but only a few have described advanced DTC. The management of MPMNs, including DTC and its particular circumstances, is reviewed, focusing on the evidence for MKI therapies. Some considerations for MPMN patients with advanced DTC are discussed, with the intention of helping physicians make decisions in these challenging situations and improving treatment and patient outcomes.


Assuntos
Adenocarcinoma , Antineoplásicos , Quinolinas , Neoplasias da Glândula Tireoide , Antineoplásicos/efeitos adversos , Humanos , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia
19.
Cancer Med ; 11 Suppl 1: 40-46, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36202609

RESUMO

Locoregional recurrence of differentiated thyroid cancer (DTC) occurs in 20% of thyroid cancer patients. Currently, there are many strategies for management of locoregional recurrence of DTC that lead to local control of the disease. The introduction of lenvatinib into the therapeutic armamentarium provides a new option for the treatment of radioiodine-refractory DTC (RR-DTC). However, results for simultaneous treatment with lenvatinib and locoregional therapies are unknown in patients with RR-DTC. This paper reviews the current status of this approach and gives recommendations on the management of lenvatinib during concomitant locoregional procedures.


Assuntos
Adenocarcinoma , Antineoplásicos , Neoplasias da Glândula Tireoide , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Humanos , Radioisótopos do Iodo/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas , Neoplasias da Glândula Tireoide/tratamento farmacológico
20.
Eur J Clin Pharmacol ; 78(12): 1973-1979, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36266366

RESUMO

AIM: To compare survival outcomes, response rates, and adverse events (AEs) in proton pump inhibitor (PPI) user and non-user patients with metastatic colorectal cancer (mCRC) treated with regorafenib. METHODS: We included 272 patients with mCRC treated with regorafenib in this study. Patients were divided into two categories according to their status of PPI use. The primary endpoint was overall survival (OS). The secondary endpoints were time to treatment failure (TTF), response rates, and safety. To exclude immortal time bias in survival analyses, we compared PPI non-user patients and all patients. RESULTS: There were 141 and 131 patients in the PPI non-user and user groups. Baseline characteristics were similar in each group. Pantoprazole was the most used PPI. At the median 35.2 (95% confidence interval (CI): 32.6-37.9) months follow-up, the median OS was similar in PPI non-user and all patients (6.9 months (95% CI: 5.3-8.5) and 7.7 months (95% CI:6.6-8.8), p = 0.913). TTF was also similar in PPI non-user and all patients (3.3 months (95% CI: 2.7-3.9) and 3.5 months (95% CI: 3.0-4.0), p = 0.661). In multivariable analysis, no statistically significant difference was observed between PPI user and non-user groups in OS and TTF (hazard ratio (HR), 0.99; 95% CI, 0.77-1.28; p = 0.963 for OS; HR, 0.93; 0.77-1.20, p = 0.598 for TTF). The objective response rates (ORR) were similar in the PPI non-user and user groups (19.8% and 16.8%, p = 0.455). The rates of any grade AEs were also similar in each group. CONCLUSION: This study found no worse outcome in the combined use of PPI and regorafenib among patients with mCRC.


Assuntos
Neoplasias Colorretais , Neoplasias Retais , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Taxa de Sobrevida , Compostos de Fenilureia/efeitos adversos , Neoplasias Retais/tratamento farmacológico
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