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1.
Medicine (Baltimore) ; 98(45): e17832, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702638

RESUMO

INTRODUCTION: The prognosis for recurrent intrahepatic cholangiocarcinoma with bone metastasis remains dismal and its treatment poses a challenge for oncologists. To date, only 2 cases were reported in which pembrolizumab, an agent against programmed cell death protein-1 (PD-1), combined with chemotherapy led to a complete response. The safety and efficacy of nivolumab-based immunotherapy combined with lenvatinibin intrahepatic cholangiocarcinoma is unknown. PATIENT CONCERNS: A 40-year-old female was identified as having a lesion of 7.0 cm in diameter in the right lobe of the liver. In addition, calculi in the main and left hepatic bile ducts as well as the gallbladder were found. DIAGNOSIS: Based on the results of imaging studies and tumor biomarker level, the patient was initially diagnosed as having intrahepatic cholangiocellular carcinoma and cholelithiasis, after which surgery was performed. The pathological examination confirmed that the tumor was cholangiocarcinoma. Adjuvant chemotherapy was administered after surgery. However, the patient developed recurrent lesions at the 5th month after surgery, and the cholangiocarcinoma expanded to the right thoracic vertebral pedicle (T7-8) at the 6th month. INTERVENTIONS: The patient underwent percutaneous microwave ablation after recurrence in the liver was identified. After that, the patient received nivolumab plus lenvatinib. OUTCOMES: The lesions in the liver decreased in size and disappeared after treatment with nivolumab plus lenvatinib. Additionally, the metastases in the right thoracic vertebral pedicle were stable after 9 months of therapy. LESSONS: Immunotherapy has revolutionized the treatment of non-small-cell lung cancer, melanoma, and advanced renal cell carcinoma. In this case, the patient achieved an excellent radiological and symptomatic response after receiving nivolumab plus lenvatinib combination therapy. Patients suffering from cholangiocarcinoma with dMMR status and a high tumor mutation burden (TMB) may have a consistent eutherapeutic effect with anti-PD-1-directed treatment.


Assuntos
Neoplasias dos Ductos Biliares/tratamento farmacológico , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Colangiocarcinoma/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Ablação por Radiofrequência , Análise de Sobrevida , Resultado do Tratamento
2.
Medicine (Baltimore) ; 98(40): e17164, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577707

RESUMO

INTRODUCTION: The PD-1 inhibitors have shown good response in the treatment for many types of malignant tumors, but as monotherapy for advanced esophageal squamous carcinoma, the objective response rate is low. Here we report a case of the patient with advanced esophageal squamous cell carcinoma (ESCC) showing a completely response to nivolumab combined with a small molecule multi-target tyrosine kinase inhibitor (TKI) anlotinib. PATIENT CONCERNS: A 61-year-old male was put under a surgery as the response to the diagnosis of ESCC in March 2014. The post-operative follow-up in March 2018 suggested a recurrence based on imagological findings, and symptoms such as shortness of breath and cough were also observed in October 2018. DIAGNOSIS: The patient was diagnosed as advanced metastatic ESCC in October 2018. INTERVENTIONS: Radical resection and esophagogastrostomy under aortic arch with left thoracotomy was performed in March 2014. As a treatment against the post-surgical recurrence, 4 courses of paclitaxel combined with nedaplatin was administered in April 2018 with an outcome of PR, followed by a combined administration of Nivolumab and anlotinib in November 2018. OUTCOMES: Chest CT during a 3-month follow-up revealed the disappearance of all the metastases, and no adverse effect was observed during the treatment. CONCLUSION: The combined treatment of nivolumab and anlotinib is likely to be considered as an optional management of advanced ESCC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Indóis/uso terapêutico , Nivolumabe/uso terapêutico , Quinolinas/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/cirurgia , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos
3.
Medicine (Baltimore) ; 98(42): e17588, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626129

RESUMO

In 2014/2015, tyrosine kinase inhibitors (TKIs) were introduced as a secondary treatment for refractory differentiated thyroid cancer (DTC) in Japan. While renal dysfunction is an adverse event of TKI, data on this adverse event in TKI-treated DTC remains insufficient. Here, we investigated renal function in patients undergoing TKI treatment for DTC and evaluated the efficacy of dose reduction/withdrawal for cases of renal dysfunction.A total of 73 cases of radioactive iodine-refractory DTC treated with sorafenib (n = 22) or lenvatinib (n = 51) were included. Patient data evaluated were TKI treatment period, estimated glomerular filtration rate (eGFR) before and after TKI therapy, incidence and degree (maximum value at time of TKI treatment) of proteinuria, and albumin levels before and after TKI therapy were compared.The mean ΔeGFR was -6.75% with lenvatinib and +5.90% with sorafenib. It was not significant (P = .15). The mean Δalbumin was -8.90% and -5.85% with lenvatinib and sorafenib, respectively; there was no significant difference between the lenvatinib and sorafenib groups (P = .77). According to our program of TKI dose reduction and withdrawal, all patients except 2 with diabetes were successfully continuing treatment.Overall, the present results demonstrated that renal function is negatively affected by long-term TKI treatment for RAI-refractory DTC. However, heightened proteinuria, decreased eGFR and albumin levels, and significant but apparently reversible renal dysfunction were more frequent with lenvatinib than sorafenib.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Radioisótopos do Iodo/uso terapêutico , Nefropatias/etiologia , Compostos de Fenilureia/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinolinas/uso terapêutico , Sorafenibe/uso terapêutico , Neoplasias da Glândula Tireoide/terapia , Idoso , Substituição de Medicamentos , Feminino , Seguimentos , Humanos , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Tolerância a Radiação , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
4.
Anticancer Res ; 39(10): 5695-5701, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570469

RESUMO

Large tumor size and arterioportal shunt are poor prognostic factors for hepatocellular carcinoma. Lenvatinib is a novel and potent multi-tyrosine kinase inhibitor developed in Japan. A 66-year-old woman with hepatocellular carcinoma and untreated hepatitis C was referred to our hospital. She was judged as unresectable and was treated with four sessions of transarterial chemoembolization; however, the therapeutic effect was unsatisfactory because of major arterioportal shunt. Lenvatinib was sequentially administered for 4 months. Thereafter, we observed tumor shrinkage, complete disappearance of arterioportal shunt, and obvious improvement in liver function. A curative conversion hepatectomy was successfully accomplished. The extremely high levels of tumor markers almost normalized; the pretreatment levels were 1,008,021 ng/ml for alpha-fetoprotein. At 1 year after the primary treatment, the patient has not experienced recurrence. To our knowledge, this is the first case of a patient with initially unresectable hepatocellular carcinoma with arterioportal shunt who underwent conversion hepatectomy after multidisciplinary treatment, including lenvatinib.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Quimioembolização Terapêutica/métodos , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , alfa-Fetoproteínas/metabolismo
5.
Medicine (Baltimore) ; 98(39): e17239, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574836

RESUMO

BACKGROUND: This study aims to evaluate the efficacy and safety of montelukast for the treatment of patients with pediatric allergic purpura (PAP). METHODS: We will retrieve the following electronic databases from inception to the present: MEDILINE, Embase, CENTRAL, CINAHL, AMED, Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, Wanfang, and VIP database without language limitation. Two authors will carry out study selection, data extraction, and quality evaluation independently. RevMan V5.3 software will be used for statistical software. RESULTS: This study will summarize high-quality evidence-based medicine to evaluate the efficacy and safety of montelukast for the treatment of PAP. CONCLUSION: This study will provide strong evidence to determine whether montelukast is an effective and safety treatment for PAP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019145472.


Assuntos
Acetatos/uso terapêutico , Púrpura de Schoenlein-Henoch/tratamento farmacológico , Quinolinas/uso terapêutico , Criança , Feminino , Humanos , Masculino , Projetos de Pesquisa , Revisão Sistemática como Assunto , Resultado do Tratamento
6.
Zhonghua Yi Xue Za Zhi ; 99(36): 2844-2847, 2019 Sep 24.
Artigo em Chinês | MEDLINE | ID: mdl-31550814

RESUMO

Objective: To evaluate the efficacy and safety of Anlotinib as a third-line therapy in patients with metastatic colorectal cancer. Methods: Anlotinib was administered to patients with advanced colorectal cancer who had received ≥ second-line standardized treatment, with 12 mg daily lasting for 2 weeks and withdrawal of drugs for a week. The relevant clinical information and treatment protocols were recorded.The efficacy and safety of anlotinib were followed up. Results: A total of 26 patients were enrolled in the study group, and 24 patients could be evaluated, including 2 cases of partial response (PR) and 16 cases of stable disease (SD).The object response rate (ORR) and disease control rate (DCR) were 8.3% and 75%, respectively. The median progression-free survival (PFS) and overall survival (OS) was 4.3 months (95% CI: 2.9-5.7 months) and 14.7 months (95% CI: 10.0-19.4 months), respectively. The most common adverse reactions were fatigue in 17 cases (17/26) and hand-foot skin reactions in 16 cases (16/26). Analysis of Kaplan-Meier revealed that without liver metastasis (95% CI: 11.7-32.3, P=0.011) and left-sided colonic cancer (95% CI: 11.7-46.1, P=0.014) were related to longer OS. Conclusion: Anlotinib as a third-line therapy for advanced colorectal cancer is feasible with high disease control rate and minor side effects.


Assuntos
Neoplasias Colorretais , Indóis/uso terapêutico , Quinolinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/tratamento farmacológico , Intervalo Livre de Doença , Humanos , Resultado do Tratamento
7.
Exp Parasitol ; 206: 107756, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31494217

RESUMO

Toxoplasma gondii is a widely distributed protozoan parasite, which affects worm-blooded animals including human. The commonest chemotherapeutics used for treatment of symptomatic toxoplasmosis have numerous adverse effects. Thus there is an eminent need to develop new therapeutic agents. Here we described the therapeutic efficacy of 4-(2-chloroquinolin-3-yl)-6-(2,5-dimethoxyphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (PPQ-8); a quinoline-related compound in a mouse model of acute and chronic toxoplasmosis. In acute infection, PPQ-8 decreased the parasite load in liver and spleen with amelioration of the hepatic and splenic pathology. In addition, recovered tachyzoites showed distorted shapes, reduced sizes, irregularities, surface protrusions, erosions and peeling besides apical region distortion when seen by scanning electron microscopy. In chronic toxoplasmosis, PPQ-8 produced degeneration and reduction of the brain cysts without stimulating a damaging inflammatory response within the brain. In both models acute and chronic, PPQ-8 prolonged the survival time of mice. These findings hold promise for the development of a novel anti-toxoplasmosis drug using PPQ-8, but further in vivo studies should be carried out to elucidate PPQ-8 mechanism of action and to report its efficacy in combination with other anti-toxoplasmosis agents.


Assuntos
Quinolinas/uso terapêutico , Toxoplasma/patogenicidade , Toxoplasmose Animal/tratamento farmacológico , Doença Aguda , Análise de Variância , Animais , Líquido Ascítico/parasitologia , Encéfalo/parasitologia , Encéfalo/patologia , Doença Crônica , Feminino , Estimativa de Kaplan-Meier , Fígado/parasitologia , Fígado/patologia , Camundongos , Microscopia Eletrônica de Varredura , Distribuição Normal , Quinolinas/síntese química , Quinolinas/química , Quinolinas/toxicidade , Distribuição Aleatória , Baço/parasitologia , Baço/patologia , Toxoplasma/efeitos dos fármacos , Toxoplasma/ultraestrutura , Toxoplasmose Animal/parasitologia
8.
Anticancer Res ; 39(9): 5149-5156, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519627

RESUMO

BACKGROUND: Factors associated with response to lenvatinib have not been clarified in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: This study retrospectively analyzed 50 patients treated with lenvatinib as first-line therapy between March 2018 and March 2019. Patients were divided into two groups by the Modified Response Evaluation Criteria in Solid Tumours (mRECIST) (responders and non-responders, whose best overall responses were complete (CR)/partial response (PR) and stable (SD)/progressive disease (PD), respectively). Factors associated with response were assessed, including the relative dose intensity 8 weeks after lenvatinib induction (8W-RDI). RESULTS: The best overall responses were 0/22/14/14 of CR/PR/SD/PD. Multivariate analysis revealed that only 8W-RDI was significantly associated with response. The receiver operating characteristic curve for 8W-RDI in differentiating responders from non-responders revealed a cut-off value of 75%. Patients with 8W-RDI ≥75% experienced a higher response rate and longer progression-free survival than patients with 8W-RDI <75%. CONCLUSION: Our results suggest that maintaining an RDI ≥75% during the initial 8 weeks of lenvatinib treatment has a favorable impact on response.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Curva ROC , Estudos Retrospectivos , Resultado do Tratamento
9.
Oncology ; 97(4): 206-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31390629

RESUMO

Lenvatinib (LEN) is a multikinase inhibitor with antiangiogenic properties recently approved in radioactive iodine-refractory differentiated thyroid cancer, hepatocellular carcinoma, and renal cell carcinoma in combination with everolimus. LEN-treated patients frequently have adverse events (AEs) that generally require such dose modifications, including drug discontinuation. Hypertension, diarrhea, weight loss, proteinuria, fatigue, and palmar-plantar erythrodysesthesia are reported among the most frequent AEs, often leading to discontinuations or dose modifications. This paper reports a case series focusing on the role of the immediate multidisciplinary approach to manage AEs.


Assuntos
Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/radioterapia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/radioterapia , Terapia Combinada/métodos , Progressão da Doença , Intervalo Livre de Doença , Everolimo/uso terapêutico , Feminino , Humanos , Radioisótopos do Iodo/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Masculino , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias da Glândula Tireoide/radioterapia , Resultado do Tratamento
10.
Oncology ; 97(5): 277-285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31307035

RESUMO

BACKGROUND/AIM: We evaluated clinical factors related to improved prognosis of unresectable hepatocellular carcinoma patients (u-HCC), who were treated with tyrosine kinase inhibitor (TKI) sequential therapy, including lenvatinib (LEN). MATERIALS/METHODS: We enrolled 84 u-HCC cases treated with TKIs including LEN from March 2018 to January 2019 (median age 71 years, 63 males, Child-Pugh score (CPS) 5/6/7 = 62/21/1, tumor-node-metastasis stage of Liver Cancer Study Group of Japan 6th (TNM-LCSGJ) II/III/IVa/IVb = 12/30/5/37, Barcelona Clinic Liver Cancer stage B/C = 33:51). Clinical findings at introduction of the initial TKI were retrospectively evaluated. RESULTS: The median albumin-bilirubin (ALBI) score at introduction of the initial TKI (sorafenib [SOR]/LEN = 80/4) was -2.56, and the past number of transarterial catheter chemoembolization was 3 (IQR: 2-5) (second-line: regorafenib [REG]/LEN/SOR = 31/49/4, third-line: LEN/REG = 31:1). The total period of administration with TKIs showed a good relationship with overall survival (OS) (r = 0.946, 95% confidence interval [CI]: 0.918-0.965, p < 0.001). The prognosis of the entire cohort was good (estimated median survival time: 46.4 months, 1-/2-/3-year OS rate [OSR] = 87.7/63.0/57.2%). A modified-ALBI grade (mALBI) of 2b (ALBI score >-2.27) was the only significant factor at the start of the initial TKI for poor prognosis (hazard ratio 2.319, 95% CI: 1.064-5.052, p = 0.034), while CPS (≥6) was not. Although there was no significant difference in TNM-LCSGJ (p = 0.213), the prognosis of patients with mALBI 1/2a (n = 66) showed better prognosis as compared to those with mALBI 2b (n = 18) (1-year/2-year/3-year OSR = 89.1/69.8/66% vs. 82.4/47.1/23.5%, p = 0.029). CONCLUSION: Good hepatic function (mALBI 1/2a) at introduction of the initial TKI is a requirement for improved prognosis of u-HCC undergoing TKI sequential therapy.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Bilirrubina/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Prognóstico , Albumina Sérica/análise
11.
Malar J ; 18(1): 231, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296223

RESUMO

BACKGROUND: Artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA/PPQ) are the recommended first- and second-line treatments, respectively, for uncomplicated falciparum malaria in Somalia. The studies reported here were conducted to assess the efficacy of these artemisinin-based combinations and the mutations in Plasmodium falciparum K13-propeller (Pfk13) domain and amplification in Pfplasmepsin 2 (Pfpm2) gene in Somalia. METHODS: One-arm prospective studies were conducted to assess the clinical and parasitological responses to DHA/PPQ and AL at two sites in 2016 and 2017, respectively, using the standard WHO protocol. The patterns of molecular markers associated with artemisinin and PPQ resistance were investigated for the first time in Somalia. RESULTS: A total of 339 patients were enrolled with 139 for AL and 200 for DHA/PPQ. With AL, no parasite recurrence was observed among patients treated at either site, corresponding to 100% clinical and parasitological responses. For DHA-PPQ, an adequate clinical and parasitological response rate > 97% was observed. All study patients on both treatments at both sites were parasite-free on day 3. Of the 138 samples with interpretable results for the polymorphism in Pfk13, only one (0.7%), from Bosaso, contained a non-synonymous mutation (R622I), which is not one of the known markers of artemisinin resistance. No Pfpm2 amplification was observed among the 135 samples with interpretable results. CONCLUSIONS: AL and DHA/PPQ were highly effective in the treatment of uncomplicated falciparum malaria, and there was no evidence of resistance to artemisinin or PPQ. These two combinations are thus relevant in the chemotherapeutic strategy for malaria control in Somalia. Trial registration ACTRN12616001005448 (Jowhar DP study), ACTRN12616000553471 (Bosaso DP study), ACTRN12617001055392 (AL study in Bosaso and Jowhar).


Assuntos
Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/prevenção & controle , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Somália , Adulto Jovem
12.
World J Gastroenterol ; 25(19): 2365-2372, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31148907

RESUMO

BACKGROUND: Lenvatinib is one of the first-line tyrosine kinase inhibitors used for unresectable hepatocellular carcinoma (HCC). In the present study, we evaluated the potential of early changes in the time-intensity curve (TIC) of arterial phase on contrast-enhanced ultrasound (CEUS) as early imaging biomarkers of lenvatinib efficacy. AIM: To evaluate the potential of the early changes in the TIC of CEUS as early imaging biomarkers of lenvatinib efficacy in patients with unresectable HCC. METHODS: We analyzed 20 consecutive patients with unresectable HCC treated with lenvatinib from March to November 2018. Tumor response at 8 wk was assessed by computed tomography using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). CEUS was performed at baseline before treatment (Day 0) and on day 7 (Day 7), and the images were analyzed in the arterial phase for 20 seconds after the contrast agent arrived at the target tumor. Three perfusion parameters were extracted from the TICs: the slope of wash-in (Slope), time to peak (TTP) intensity, and the total area under the curve (AUC) during wash-in. The rate of change in the TIC parameters between Day 0 and Day 7 was compared between treatment responders and non-responders based on mRECIST. RESULTS: The rate of change for all TIC parameters showed significant differences between the responders (n = 9) and non-responders (n = 11) (Slope, P = 0.025; TTP, P = 0.004; and AUC, P = 0.0003). The area under the receiver operating curve values for slope, TTP, and AUC for the prediction of responders were 0.805, 0.869, and 0.939, respectively. CONCLUSION: CEUS may be useful for the early prediction of tumor response to lenvatinib therapy in patients with unresectable HCC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Imagem de Perfusão/métodos , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Artérias/diagnóstico por imagem , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Feminino , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Critérios de Avaliação de Resposta em Tumores Sólidos , Tomografia Computadorizada por Raios X , Ultrassonografia/métodos
13.
Oncology ; 97(2): 75-81, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31242488

RESUMO

AIM: This study investigated early tumor marker response and treatment response in patients with advanced hepatocellular carcinoma (HCC) treated with lenvatinib. METHODS: Twenty patients with advanced HCC who received lenvatinib were enrolled in this retrospective study. α-Fetoprotein (AFP) and des-γ-carboxyprothrombin (DCP) levels were measured before treatment as well as 2 and 4 weeks after treatment. The objective response rate was evaluated by mRECIST at 6 weeks. RESULTS: The response rate was 30% (complete response/partial response/stable disease/progressive disease: n = 0/6/6/8 cases) by mRECIST. At 4 weeks, the AFP levels of 12 patients (80%) were lower than at baseline. The AFP levels of 9 patients (60%) continued decreasing from 2 weeks to 4 weeks (sustained-reduction group). In this group, the response rate was 67%. The median AFP change rate was -39% at 4 weeks. In imaging responders, the AFP change rate significantly decreased (p = 0.02). The DCP change rate had no significant correlation with imaging response. The AFP-sustained-reduction group had significantly higher adherence to lenvatinib than the non-sustained-reduction group (p = 0.02). CONCLUSION: With lenvatinib therapy for HCC, the AFP levels of most patients had declined at 2 weeks, and at 4 weeks the AFP-sustained-reduction group demonstrated a higher objective response.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Biomarcadores/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Precursores de Proteínas/metabolismo , Protrombina/metabolismo , Quinolinas/uso terapêutico , alfa-Fetoproteínas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/metabolismo , Quimioembolização Terapêutica , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
14.
BMC Cancer ; 19(1): 582, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200667

RESUMO

BACKGROUND: Thyroid cancer is the most common endocrine malignancy. Some advanced disease is, or becomes, resistant to radioactive iodine therapy (refractory disease); this holds poor prognosis of 10% 10-year overall survival. Whilst Sorafenib and Lenvatinib are now licenced for the treatment of progressive iodine refractory thyroid cancer, these treatments require continuing treatment and can be associated with significant toxicity. Evidence from a pilot study has demonstrated feasibility of Selumetinib to allow the reintroduction of I-131 therapy; this larger, multicentre study is required to demonstrate the broader clinical impact of this approach before progression to a confirmatory trial. METHODS: SEL-I-METRY is a UK, single-arm, multi-centre, two-stage phase II trial. Participants with locally advanced or metastatic differentiated thyroid cancer with at least one measureable lesion and iodine refractory disease will be recruited from eight NHS Hospitals and treated with four-weeks of oral Selumetinib and assessed for sufficient I-123 uptake (defined as any uptake in a lesion with no previous uptake or 30% or greater increase in uptake). Those with sufficient uptake will be treated with I-131 and followed for clinical outcomes. Radiation absorbed doses will be predicted from I-123 SPECT/CT and verified from scans following the therapy. Sixty patients will be recruited to assess the primary objective of whether the treatment schedule leads to increased progression-free survival compared to historical control data. DISCUSSION: The SEL-I-METRY trial will investigate the effect of Selumetinib followed by I-131 therapy on progression-free survival in radioiodine refractory patients with differentiated thyroid cancer showing increased radioiodine uptake following initial treatment with Selumetinib. In addition, information on toxicity and dosimetry will be collected. This study presents an unprecedented opportunity to investigate the role of lesional dosimetry in molecular radiotherapy, leading to greater personalisation of therapy. To date this has been a neglected area of research. The findings of this trial will be useful to healthcare professionals and patients alike to determine whether further study of this agent is warranted. It is hoped that the development of the infrastructure to deliver a multicentre trial involving molecular radiotherapy dosimetry will lead to further trials in this field. TRIAL REGISTRATION: SEL-I-METRY is registered under ISRCTN17468602 , 02/12/2015.


Assuntos
Antineoplásicos/uso terapêutico , Benzimidazóis/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Antineoplásicos/efeitos adversos , Benzimidazóis/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Humanos , Terapia de Alvo Molecular , Estudos Multicêntricos como Assunto , Metástase Neoplásica , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Sorafenibe/efeitos adversos , Sorafenibe/uso terapêutico , Neoplasias da Glândula Tireoide/patologia , Reino Unido
15.
Eur J Med Chem ; 178: 154-167, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31181480

RESUMO

A series of new quinoline derivatives was designed, synthesized and evaluated for their antiproliferative activity. The results demonstrated that compounds 11p, 11s, 11v, 11x and 11y exhibited potent antiproliferative activity with IC50 value of lower than 10 µM against seven human tumor cell lines, and N-(3-methoxyphenyl)-7- (3-phenylpropoxy)quinolin-4-amine 11x was found to be the most potent antiproliferative agent against HCT-116, RKO, A2780 and Hela cell lines with an IC50 value of 2.56, 3.67, 3.46 and 2.71 µM, respectively. The antitumor efficacy of the representative compound 11x in mice was also evaluated, and the results showed that compound 11x effectively inhibited tumor growth and decreased tumor weight in animal models. Further investigation on mechanism of action indicated that compound 11x could inhibit colorectal cancer growth through ATG5-depenent autophagy pathway. Therefore, these quinoline derivatives are a new class of molecules that have the potential to be developed as new antitumor drugs.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Quinolinas/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína 5 Relacionada à Autofagia/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Camundongos Endogâmicos BALB C , Estrutura Molecular , Quinolinas/síntese química , Quinolinas/química , Quinolinas/farmacologia , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Bull Cancer ; 106(9): 812-819, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31200896

RESUMO

Patients with radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC) represent a challenging subgroup of DTC because they are at higher risk of cancer-related death. Multidisciplinary discussions can assess the role and the nature of local treatments, but also determine the optimal timing for first-line antiangiogenic therapy as some of these patients can be followed for several months or years without any treatment. In this review, we will examine the definition of RAIR-DTC, the different treatment options and finally some of the most recent cancer research breakthroughs for RAIR-DTC.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Tolerância a Radiação , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Imunoterapia , Pessoa de Meia-Idade , Meta-Análise em Rede , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Sorafenibe/uso terapêutico , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia
18.
Rev Soc Bras Med Trop ; 52: e20180453, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31141053

RESUMO

INTRODUCTION: Concern regarding the cardiotoxicity of antimalarials has been renewed because of their potential to cause QT/QTc interval prolongation related to torsade de pointes (TdP). Artemisinin-piperaquine (AP) is considered an effective artemisinin-based combination therapy (ACT) for malaria. METHODS: This study involved a retrospective analysis of clinical data of 93 hospitalized malaria patients who had received AP orally. Electrocardiograms (ECGs) were obtained at specific time points in the original study. RESULTS: Some cases of QT prolongation were observed. However, no TdP was found. CONCLUSIONS: AP may cause QT interval prolongation in some malaria patients but may not lead to TdP.


Assuntos
Antimaláricos/efeitos adversos , Artemisininas/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Malária Falciparum/tratamento farmacológico , Quinolinas/efeitos adversos , Adulto , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Quimioterapia Combinada , Eletrocardiografia , Feminino , Humanos , Síndrome do QT Longo/diagnóstico , Masculino , Pessoa de Meia-Idade , Quinolinas/uso terapêutico , Estudos Retrospectivos
19.
Drugs Today (Barc) ; 55(5): 305-313, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31131841

RESUMO

Hepatocellular carcinoma (HCC) is a worldwide healthcare problem, with a rising incidence. In its advanced stage, the prognosis of untreated HCC is very poor. Only in 2007, after a long series of failed trials, the multi-tyrosine kinase inhibitor sorafenib demonstrated its superiority over placebo, becoming the first approved frontline therapy for advanced HCC. For a decade, all of the frontline trials using sorafenib as a comparator systematically failed, leaving this drug as the only available treatment in this setting. In 2018, lenvatinib mesylate (another multitarget tyrosine kinase inhibitor) demonstrated noninferiority compared to sorafenib in the phase III, randomized, controlled REFLECT trial. Currently, lenvatinib represents the only available alternative to sorafenib as a frontline systemic treatment of advanced HCC. In this monograph, we review the main preclinical and clinical evidence that emerged in the trials of lenvatinib, with particular attention to the features differentiating this drug from sorafenib.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Humanos , Mesilatos , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Medicine (Baltimore) ; 98(22): e15749, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145289

RESUMO

RATIONALE: Glioblastoma (GBM) is the most aggressive malignant brain tumor in adults. The first choice for GBM is surgery, and followed by a combination of radiotherapy and chemotherapy. There are limited treatments for patients with recurrent GBM. Relapsed patients usually have a worse prognosis, and with a median survival time of <6 months. Anlotinib is a novel small molecule multi-target tyrosine kinase inhibitor that can inhibit tumor angiogenesis and inhibit tumor cell growth. This drug has been used to treat advanced lung cancer. PATIENT CONCERNS: We present a case of recurrent GBM was treated with anlotinib in this report. The patient was diagnosed with GBM in August 2016 and treated with surgery and temozolomide (TMZ) chemotherapy. She was diagnosed with recurrence in February 2017 following which she was treated with gamma knife and TMZ chemotherapy. In November 2017, the patient presented with decreased vision in left eye. She was given radiation and her left eye vision returned to normal after radiation. On May23, 2018, the patient reported a decrease in left visual acuity again. DIAGNOSES: Brain magnetic resonance imaging (MRI) showed progression of the disease, and the tumor invaded the left optic nerve. INTERVENTIONS: This patient was administer anlotinib 12 mg po qd (d1-14, 21days as a cycle). Three cycles anlotinib were given to this patient. OUTCOMES: The patient reported her left visual acuity increased over 10 days after first cycle of anlotinib treatment. MRI scan revealed tumor volume shrinks, especially the part that invades the left optic nerve shrinks significantly at 26 days after anlotinib treatment on August 11, 2018. However, the tumor progressed in 2 months after using of anlotinib. From the beginning of the application of anlotinib to death, her survival time was 110 days. LESSONS: Anlotinib treatment with mild side effects may be a new option for the patients with recurrent glioblastoma.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Indóis/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Quinolinas/uso terapêutico , Neoplasias Encefálicas/patologia , Evolução Fatal , Feminino , Glioblastoma/patologia , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/patologia
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