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1.
Medicine (Baltimore) ; 99(52): e23453, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350727

RESUMO

BACKGROUND: Bronchial asthma (BA) is a chronic airway inflammatory disease with reversible airflow limitation as the main clinical manifestations, such as wheezing, cough, shortness of breath, chest tightness, etc, mediated by a variety of inflammatory cells, which can be recurrent. Clinical can improve symptoms, but cannot be cured; glucocorticoid is the most important first-line medication. Clinical practice has shown that montelukast sodium combined with fluticasone in the treatment of adult BA can improve clinical efficacy and reduce adverse reactions. The purpose of this study is to systematically study the efficacy and safety of montelukast sodium combined with fluticasone in the treatment of adult BA. METHODS: The Chinese databases (CNKI, VIP, Wanfang, Chinese Biomedical Database) and English databases (PubMed, the Cochrane Library, Embase, Web of Science) were searched by computer, for the randomized controlled clinical studies of montelukast sodium combined with fluticasone in the treatment of adult BA from establishment of database to October 2020. Two researchers independently extracted the relevant data and evaluated the quality of the literatures, and used RevMan5.3 software to conduct meta-analyze of the included literatures. RESULTS: This study assessed the efficacy and safety of montelukast sodium combined with fluticasone in the treatment of adult BA through total effective rate, pulmonary function (FEV1, FVC, PEF, FEV1/FVC), and adverse reactions. CONCLUSION: This study will provide reliable evidence-based evidence for the clinical application of montelukast sodium combined with fluticasone in the treatment of adult BA. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/CKQFM.


Assuntos
Acetatos/administração & dosagem , Antiasmáticos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Asma/tratamento farmacológico , Ciclopropanos/administração & dosagem , Fluticasona/administração & dosagem , Metanálise como Assunto , Quinolinas/administração & dosagem , Projetos de Pesquisa , Sulfetos/administração & dosagem , Revisões Sistemáticas como Assunto/métodos , Acetatos/efeitos adversos , Adulto , Antiasmáticos/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Ciclopropanos/efeitos adversos , Combinação de Medicamentos , Fluticasona/efeitos adversos , Humanos , Quinolinas/efeitos adversos , Sulfetos/efeitos adversos , Resultado do Tratamento
2.
Cochrane Database Syst Rev ; 10: CD012796, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33058158

RESUMO

BACKGROUND: Several comparative randomised controlled trials (RCTs) have been performed including combinations of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors since the publication of a Cochrane Review on targeted therapy for metastatic renal cell carcinoma (mRCC) in 2008. This review represents an update of that original review. OBJECTIVES: To assess the effects of targeted therapies for clear cell mRCC in patients naïve to systemic therapy. SEARCH METHODS: We performed a comprehensive search with no restrictions on language or publication status. The date of the latest search was 18 June 2020. SELECTION CRITERIA: We included randomised controlled trials, recruiting patients with clear cell mRCC naïve to previous systemic treatment. The index intervention was any TKI-based targeted therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the included studies and extracted data for the primary outcomes: progression-free survival (PFS), overall survival (OS) and serious adverse events (SAEs); and the secondary outcomes: health-related quality of life (QoL), response rate and minor adverse events (AEs). We performed statistical analyses using a random-effects model and rated the certainty of evidence according to the GRADE approach. MAIN RESULTS: We included 18 RCTs reporting on 11,590 participants randomised across 18 comparisons. This abstract focuses on the primary outcomes of select comparisons. 1. Pazopanib versus sunitinib Pazopanib may result in little to no difference in PFS as compared to sunitinib (hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.90 to 1.23; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 420 per 1000 in this trial at 12 months, this corresponds to 18 fewer participants experiencing PFS (95% CI 76 fewer to 38 more) per 1000 participants. Pazopanib may result in little to no difference in OS compared to sunitinib (HR 0.92, 95% CI 0.80 to 1.06; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 27 more OSs (95% CI 19 fewer to 70 more) per 1000 participants. Pazopanib may result in little to no difference in SAEs as compared to sunitinib (risk ratio (RR) 1.01, 95% CI 0.94 to 1.09; 1 study, 1102 participants; low-certainty evidence). Based on the control event risk of 734 per 1000 in this trial, this corresponds to 7 more participants experiencing SAEs (95% CI 44 fewer to 66 more) per 1000 participants. 2. Sunitinib versus avelumab and axitinib Sunitinib probably reduces PFS as compared to avelumab plus axitinib (HR 1.45, 95% CI 1.17 to 1.80; 1 study, 886 participants; moderate-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 130 fewer participants experiencing PFS (95% CI 209 fewer to 53 fewer) per 1000 participants. Sunitinib may result in little to no difference in OS (HR 1.28, 95% CI 0.92 to 1.79; 1 study, 886 participants; low-certainty evidence). Based on the control event risk of 890 per 1000 in this trial at 12 months, this would result in 29 fewer OSs (95% CI 78 fewer to 8 more) per 1000 participants. Sunitinib may result in little to no difference in SAEs (RR 1.01, 95% CI 0.93 to 1.10; 1 study, 873 participants; low-certainty evidence). Based on the control event risk of 705 per 1000 in this trial, this corresponds to 7 more SAEs (95% CI 49 fewer to 71 more) per 1000 participants.  3. Sunitinib versus pembrolizumab and axitinib Sunitinib probably reduces PFS as compared to pembrolizumab plus axitinib (HR 1.45, 95% CI 1.19 to 1.76; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 590 per 1000 in this trial at 12 months, this corresponds to 125 fewer participants experiencing PFS (95% CI 195 fewer to 56 fewer) per 1000 participants. Sunitinib probably reduces OS (HR 1.90, 95% CI 1.36 to 2.65; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 880 per 1000 in this trial at 12 months, this would result in 96 fewer OSs (95% CI 167 fewer to 40 fewer) per 1000 participants. Sunitinib may reduce SAEs as compared to pembrolizumab plus axitinib (RR 0.90, 95% CI 0.81 to 1.02; 1 study, 854 participants; low-certainty evidence) although the CI includes the possibility of no effect. Based on the control event risk of 604 per 1000 in this trial, this corresponds to 60 fewer SAEs (95% CI 115 fewer to 12 more) per 1000 participants.  4. Sunitinib versus nivolumab and ipilimumab Sunitinib may reduce PFS as compared to nivolumab plus ipilimumab (HR 1.30, 95% CI 1.11 to 1.52; 1 study, 847 participants; low-certainty evidence). Based on the control event risk of 280 per 1000 in this trial at 30 months' follow-up, this corresponds to 89 fewer PFSs (95% CI 136 fewer to 37 fewer) per 1000 participants. Sunitinib reduces OS (HR 1.52, 95% CI 1.23 to 1.89; 1 study, 847 participants; high-certainty evidence). Based on the control event risk 600 per 1000 in this trial at 30 months, this would result in 140 fewer OSs (95% CI 219 fewer to 67 fewer) per 1000 participants. Sunitinib probably increases SAEs (RR 1.37, 95% CI 1.22 to 1.53; 1 study, 1082 participants; moderate-certainty evidence). Based on the control event risk of 457 per 1000 in this trial, this corresponds to 169 more SAEs (95% CI 101 more to 242 more) per 1000 participants. AUTHORS' CONCLUSIONS: Based on the low to high certainty of evidence, several combinations of immune checkpoint inhibitors appear to be superior to single-agent targeted therapy in terms of PFS and OS, and with a favourable AE profile. Some single-agent targeted therapies demonstrated a similar or improved oncological outcome compared to others; minor differences were observed for AE within this group. The certainty of evidence was variable ranging from high to very low and all comparisons were based on single trials.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Axitinibe/efeitos adversos , Axitinibe/uso terapêutico , Bevacizumab/efeitos adversos , Bevacizumab/uso terapêutico , Viés , Carcinoma de Células Renais/mortalidade , Everolimo/efeitos adversos , Everolimo/uso terapêutico , Humanos , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Qualidade de Vida , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Sirolimo/efeitos adversos , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , Sorafenibe/efeitos adversos , Sorafenibe/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Sunitinibe/efeitos adversos , Sunitinibe/uso terapêutico
3.
Medicine (Baltimore) ; 99(40): e22572, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019469

RESUMO

RATIONALE: Atorvastatin is the most common drug used in therapy for cardiovascular diseases. The most common adverse side effects associated with statins are myopathy and hypertransaminasemia. Here, we report a rare case of gamma glutamyl transpeptidase (GGT) elevation induced by atorvastatin. PATIENT CONCERNS: A 47-year-old male was admitted to our hospital with dyslipidemia, he had been taking pitavastatin 2 mg/day for 2 months. The levels of total cholesterol (265.28 mg/dL) and low-density lipoprotein-cholesterol (LDL) (179.15 mg/dL) were also high. DIAGNOSIS: Blood lipid test showed mixed dyslipidemia. INTERVENTION: Atorvastatin 10 mg/day was given to the patient. OUTCOMES: The patient came back to our hospital for blood tests after 4 weeks. Although no symptoms were detectable, the patient's GGT level was markedly elevated (up to 6-fold over normal level) with less marked increases in alkaline phosphatase (ALP) and alanine aminotransferase (ALT). The serum GGT level returned to normal within 6 weeks of cessation of atorvastatin. LESSONS: This is a case of GGT elevation without hyperbilirubinemia, hypertransaminasemiam, or serum creatine phosphokinase (CPK) abnormalities despite an atorvastatin regimen. This case highlights GGT elevation caused by atorvastatin, a rare but serious condition. Clinicians should be aware of these possible adverse effects and monitor liver function tests in patients on statin therapy.


Assuntos
Atorvastatina/efeitos adversos , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Quinolinas/efeitos adversos , gama-Glutamiltransferase/efeitos dos fármacos , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Atorvastatina/administração & dosagem , Atorvastatina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/diagnóstico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Suspensão de Tratamento , gama-Glutamiltransferase/sangue
4.
Anticancer Res ; 40(9): 5271-5276, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878816

RESUMO

BACKGROUND/AIM: Hepatic encephalopathy is an adverse event resulting from lenvatinib use in patients with hepatocellular carcinoma (HCC). We analyzed the influence of lenvatinib on portal venous flow velocity (PVV) and serum ammonia concentration. PATIENTS AND METHODS: Eleven patients with unresectable HCC were enrolled, including three with modified albumin-bilirubin (mALBI) grade 1, three with grade 2a, and five with grade 2b. PVV was measured by Doppler ultrasound sonography before and on day 2 of administration. RESULTS: Out of 11 patients, one developed hepatic encephalopathy. PVV was reduced in 10 patients, and the change from baseline was significantly correlated with lenvatinib dosage. The increase in serum ammonia concentration was affected by lenvatinib dose and baseline hepatic function as a threshold between mALBI grade 2a and 2b statistically. There was no correlation between changes in PVV and serum ammonia concentration. CONCLUSION: Lenvatinib might directly disturb hepatocyte metabolism to result in increased serum ammonia concentration.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Hiperamonemia/etiologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Bilirrubina/sangue , Carcinoma Hepatocelular/diagnóstico , Suscetibilidade a Doenças , Feminino , Encefalopatia Hepática/diagnóstico , Encefalopatia Hepática/etiologia , Humanos , Hiperamonemia/diagnóstico , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Veia Porta/fisiopatologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Fatores de Risco
5.
PLoS Negl Trop Dis ; 14(9): e0008619, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32966290

RESUMO

BACKGROUND: Despite the reported success in reducing morbidity, praziquantel alone is insufficient for the control and elimination of schistosomiasis, partly due to its poor efficacy against the juvenile worms. Artemisinin derivatives are effective against juvenile worms but are less effective against adult worms. We compared the safety and efficacy of praziquantel and Dihydroartemisinin-piperaquine combination against the standard praziquantel alone for treatment of intestinal schistosomiasis. METHODS: In this randomized, open-label, non-inferiority trial, 639 Schistosoma mansoni infected children were enrolled and randomized to receive either praziquantel alone or praziquantel plus Dihydroartemisinin-piperaquine combination. Two stool samples were collected on consecutive days at baseline, 3 and 8 weeks post-treatment and analyzed using thick smear Kato Katz method. Efficacy was assessed by cure and egg reduction rates at 3 and 8 weeks post-treatment. Adverse events were assessed within four hours of drugs intake. The primary outcome was cure rates at 8 weeks of post-treatment. Secondary outcomes were egg reduction rates at 8 weeks of post-treatment and treatment-associated adverse events. RESULTS: At 3 weeks of post-treatment, cure rates were 88.3% (263/298, 95% CI = 84.1%- 91.4%) and 81.2% (277/341, 95% CI = 76.7%- 85.0%) for the combination therapy and praziquantel alone, respectively (p < 0.01, odds ratio (OR) = 1.74, 95% CI of OR = 1.11 to 2.69). At 8 weeks, there was a significant drop in the cure rates in praziquantel alone group to 63.9% (218/341, 95% CI = 58.7%- 68.8%) compared to 81.9% (244/298, 95% CI = 77.1%- 85.8%) in the combination therapy group (p < 0.0001, OR = 2.55, 95%CI of OR = 1.75 to 3.69). Egg reduction rates at 8 weeks post-treatment were significantly higher in the combination therapy group 93.6% (95% CI = 90.8%- 96.4%) compared to 87.9% (95% CI = 84.4%- 91.4%) in the praziquantel only group (p = 0.01). On both Univariate and Multivariate regression analysis, type of treatment received was a significant predictor of cure at week 8 post-treatment. Overall, 30.8% (95% CI = 27.2%- 34.4%) of the study participants experienced mild and transient treatment-associated adverse events, post-treatment abdominal pain (27.1%) being the most common adverse event observed. There was no significant difference in the overall occurrence of adverse events between the two treatment groups. CONCLUSION: Praziquantel and Dihydroartemisinin piperaquine combination therapy is safe, and more efficacious compared to praziquantel alone for the treatment of intestinal schistosomiasis. Further studies are needed to explore if the combination therapy can be considered as an option for mass drug administration to control and eventually eliminate schistosomiasis.


Assuntos
Anti-Helmínticos/uso terapêutico , Artemisininas/uso terapêutico , Praziquantel/uso terapêutico , Quinolinas/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Adolescente , Animais , Anti-Helmínticos/efeitos adversos , Artemisininas/efeitos adversos , Criança , Quimioterapia Combinada , Fezes/parasitologia , Feminino , Humanos , Intestinos/parasitologia , Masculino , Praziquantel/efeitos adversos , Quinolinas/efeitos adversos , Schistosoma mansoni/efeitos dos fármacos , Tanzânia , Resultado do Tratamento
6.
Lancet Oncol ; 21(6): 843-850, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32502444

RESUMO

BACKGROUND: Thymic carcinoma is a rare malignant disease and standard treatment for advanced or metastatic thymic carcinoma previously treated with platinum-based chemotherapy has not been established. Lenvatinib is a novel multi-targeted inhibitor of VEGFR, FGFR, RET, c-Kit, and other kinases. The aim of this trial was to assess the activity and safety of lenvatinib as a second-line treatment in thymic carcinoma. METHODS: This single-arm, phase 2 trial done in eight institutions in Japan (five cancer centres, two medical university hospitals, and one public hospital) enrolled patients with pathologically confirmed unresectable advanced or metastatic thymic carcinoma that progressed following at least one platinum-based chemotherapy. Key inclusion criteria were age 20 years or older, at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors version 1.1, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 24 mg of lenvatinib orally once daily in 4-week cycles until disease progression or occurrence of unacceptable adverse events. The primary endpoint was objective response rate evaluated at the data cutoff date (Feb 22, 2019), by independent central review in the intention-to-treat population. This trial is registered on JMACCT, JMA-IIA00285, and on UMIN-CTR, UMIN000026777. FINDINGS: Between April 21, 2017, and Feb 22, 2018, 42 patients were enrolled and all patients were included in the activity and safety analysis. The median follow-up period was 15·5 months (IQR 13·1-17·5). The objective response rate was 38% (90% CI 25·6-52·0, p<0·0001). 16 (38%) of 42 patients had a partial response and 24 (57%) had stable disease. The most frequent grade 3 treatment-related adverse events were hypertension (27 [64%]) and palmar-plantar erythrodysaesthesia syndrome (three [7%]). No patient died from adverse events. INTERPRETATION: The activity and safety of lenvatinib in patients with advanced or metastatic thymic carcinoma was confirmed. These results suggest that lenvatinib could become a standard treatment option for patients with previously treated advanced or metastatic thymic carcinoma. FUNDING: Center for Clinical Trials, Japan Medical Association.


Assuntos
Antineoplásicos/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Quinolinas/administração & dosagem , Timoma/tratamento farmacológico , Neoplasias do Timo/tratamento farmacológico , Idoso , Antineoplásicos/efeitos adversos , Progressão da Doença , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/efeitos adversos , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Timoma/enzimologia , Timoma/mortalidade , Timoma/secundário , Neoplasias do Timo/enzimologia , Neoplasias do Timo/mortalidade , Neoplasias do Timo/patologia , Fatores de Tempo
7.
J Cardiovasc Pharmacol Ther ; 25(6): 548-555, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32567339

RESUMO

BACKGROUND: Controversy remains regarding the influence of lipid-lowering therapy on the eicosapentaenoic acid/arachidonic acid ratio. OBJECTIVE: This study aimed to clarify the effects of lipid-lowering therapy on the eicosapentaenoic acid/arachidonic acid ratio in patients with acute coronary syndrome (ACS). METHODS: This was a post hoc sub-analysis of the Heart Institute of Japan-PRoper level of lipid-lowering with pitavastatin and ezetimibe in ACS study. We compared the eicosapentaenoic acid/arachidonic acid ratio changes from baseline to the 3-month follow-up after contemporary lipid-lowering therapy with pitavastatin + ezetimibe therapy and pitavastatin mono-therapy. RESULTS: Among patients with ACS and dyslipidemia, the eicosapentaenoic acid/arachidonic acid increased significantly in the pitavastatin mono-therapy group (0.40 ± 0.26 to 0.46 ± 0.34, P < .0001) but did not increase in the pitavastatin + ezetimibe group (0.37 ± 0.22 to 0.38 ± 0.27, P = .18). When the analysis was limited to patients who received 2 mg/day of pitavastatin during the follow-up period, these trends in changes of the eicosapentaenoic acid/arachidonic acid ratio remained unchanged. Multivariate analysis showed that ezetimibe use (P = .005; ß = 0.09), ST-elevation myocardial infarction (P = .04; ß = -0.01), and baseline low-density lipoprotein cholesterol (LDL-C) level (P = .0003; ß = 0.12) were independent predictors of the percentage change in the eicosapentaenoic acid/arachidonic acid ratio. These trends were similar even when the analysis was limited to patients who did not take statins at enrollment. CONCLUSION: Standard lipid-lowering therapy with pitavastatin mono-therapy improved the eicosapentaenoic acid/arachidonic acid ratio for patients with ACS. Intensive lipid-lowering therapy with pitavastatin + ezetimibe did not improve the eicosapentaenoic acid/arachidonic acid ratio, although LDL-C decreased significantly. Inhibition of the improvement in the eicosapentaenoic acid/arachidonic acid ratio by adding ezetimibe may affect cardiovascular disease prognosis.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Anticolesterolemiantes/uso terapêutico , Ácido Araquidônico/sangue , Ácido Eicosapentaenoico/sangue , Ezetimiba/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Quinolinas/uso terapêutico , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Idoso , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Ezetimiba/efeitos adversos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Quinolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
8.
Medicine (Baltimore) ; 99(25): e20596, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569187

RESUMO

BACKGROUND: Whether erlotinib plus tivantinib (ET) can achieve better clinical benefits than erlotinib plus placebo (EP) among participants with previously treated advanced non-small-cell lung cancer (NSCLC) is still disputed. We conducted a meta-analysis to evaluate the anticancer efficacy and safety of both regimens. MATERIALS AND METHODS: We searched for pertinent trials at PubMed, ScienceDirect, The Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar. Endpoints mainly included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). RESULTS: We included 1522 patients who previously received ≥1 systemic anti-cancer regimen that included platinum-based chemotherapy. Although ET failed to improve OS (hazard ratio [HR] = 0.91, 95% confidence interval [CI]: 0.75-1.10, P = .35), the ET group had better PFS (HR = 0.73, 95% CI: 0.67-0.80, P < .00001), higher ORR (HR = 1.50, 95% CI: 1.06-2.12, P = .02), and better DCR (HR = 1.38, 95% CI: 1.20-1.59, P < .00001). Our subanalysis suggested that the ET group may have had better OS among patients with high Mesenchymal to epithelial transition factor (MET) expression (HR = 0.76, 95% CI: 0.58-0.99, P = .04) and good VeriStrat (HR = 0.88, 95% CI: 0.83-0.93, P < .0001). AEs were roughly similar except for specific hematological toxicities: more neutropenia and febrile neutropenia were observed in the ET group, both of which should not be overlooked. CONCLUSIONS: ET appears to be superior to EP due to better PFS and higher response rates, especially for patients with high MET expression and good VeriStrat. The greater hematological toxicity in the ET regimen is non-negligible.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Pirrolidinonas/administração & dosagem , Quinolinas/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Erlotinib/efeitos adversos , Humanos , Intervalo Livre de Progressão , Pirrolidinonas/efeitos adversos , Quinolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Leukemia ; 34(8): 2125-2137, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32572189

RESUMO

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs.


Assuntos
Compostos de Anilina/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Nitrilos/uso terapêutico , Quinolinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/efeitos adversos , Feminino , Humanos , Leucemia Mieloide de Fase Crônica/genética , Leucemia Mieloide de Fase Crônica/psicologia , Masculino , Pessoa de Meia-Idade , Nitrilos/efeitos adversos , Cromossomo Filadélfia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Qualidade de Vida , Quinolinas/efeitos adversos
12.
Lancet Oncol ; 21(8): 1057-1065, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32589866

RESUMO

BACKGROUND: Pembrolizumab, an anti-PD-1 antibody, results in tumour response in around 15% of patients with advanced gastric cancer who have a PD-L1 combined positive score of at least 1. Lenvatinib, a multikinase inhibitor of VEGF receptors and other receptor tyrosine kinases, substantially decreased tumour-associated macrophages and increased infiltration of CD8 T cells, resulting in enhanced anti-tumour activity of PD-1 inhibitors in an in-vivo model. We aimed to assess the combination of lenvatinib plus pembrolizumab in patients with advanced gastric cancer in a phase 2 study. METHODS: This study was an open-label, single-arm, phase 2 trial undertaken at the National Cancer Center Hospital East (Chiba, Japan). Eligible patients were aged 20 years or older and had metastatic or recurrent adenocarcinoma of the stomach or gastro-oesophageal junction, an Eastern Cooperative Oncology Group performance status of 0 or 1, and measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1), irrespective of the number of previous lines of treatment. Patients received 20 mg oral lenvatinib daily plus 200 mg intravenous pembrolizumab every 3 weeks until disease progression, development of intolerable toxicity, or withdrawal of consent. The primary endpoint was objective response rate according to RECIST, analysed in all patients who were eligible and received protocol treatment at least once. The safety analysis included all those who received protocol treatment at least once, regardless of eligibility. This study is registered at ClinicalTrials.gov, NCT03609359, and enrolment is complete. FINDINGS: Between Oct 15, 2018, and March 25, 2019, 29 patients were enrolled in the first-line or second-line settings. At data cutoff (March 20, 2020), the median follow-up was 12·6 months (IQR 10·5-14·3). 20 (69%, 95% CI 49-85) of 29 patients had an objective response. The most common grade 3 treatment-related adverse events were hypertension (in 11 [38%] patients), proteinuria (five [17%]), and platelet count decrease (two [7%]). No grade 4 treatment-related adverse events, serious treatment-related adverse events, or treatment-related deaths occurred. INTERPRETATION: Lenvatinib plus pembrolizumab showed promising anti-tumour activity with an acceptable safety profile in patients with advanced gastric cancer. On the basis of these results, a confirmatory trial will be planned in the future. FUNDING: Merck Sharp & Dohme.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos
13.
Int J Clin Oncol ; 25(8): 1492-1498, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32447474

RESUMO

BACKGROUND: The ALTER 0303 study showed that anlotinib can significantly improve overall survival (OS) compared with the placebo in advanced non-small-cell lung cancer (NSCLC). Hand-foot syndrome (HFS) is a common anlotinib-related adverse event. The aim of this study was to assess the association of HFS with clinical benefit. METHODS: A subgroup analysis of patients treated with anlotinib from the ALTER 0303 study was performed. Our analysis assessed if the appearance of anlotinib-related HFS in the first 42 days (second-cycle HFS) and at any time could produce better clinical benefits. RESULTS: In this study, 294 patients were treated with anlotinib. Of which, 129 patients had HFS at any time, and 76 patients developed HFS in the first 2 cycles. Patients who received anlotinib and developed HFS had significantly prolonged OS, progression-free survival (PFS) compared to those who did not develop HFS in the first 2 cycles (13.5 vs 8.7 months, p = 0.001; adjusted hazard ratio (HR) 0.63 (95% confidence interval [CI] 0.44-0.89), p = 0.009; 5.8 vs 4.5 months, p = 0.001; adjusted HR, 0.59 [0.43-0.81], p = 0.001). The significant OS and PFS benefits for patients with HFS versus without were seen at any time (14.5 vs 7.3 months, p = 0.000; adjusted HR, 0.50 [0.36-0.67], p = 0.000; 5.8 vs 4.2 months, p = 0.000; adjusted HR, 0.49 [0.37-0.65], p = 0.000). In addition, the grade of severity of HFS was strongly correlated with OS (p = 0.000). CONCLUSION: Presence of HFS may be a potential clinical marker for the treatment of NSCLC with anlotinib.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Síndrome Mão-Pé/etiologia , Indóis/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Quinolinas/efeitos adversos , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Indóis/uso terapêutico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Quinolinas/uso terapêutico , Resultado do Tratamento
14.
Int J Clin Oncol ; 25(7): 1278-1284, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32347432

RESUMO

BACKGROUND: Proteinuria induced by lenvatinib is a class effect that occurs secondary to VEGFR suppression. Withholding of lenvatinib is required in cases with severe proteinuria. Urine protein-creatinine ratio (UPCR, g/gCre) has recently attracted attention as an alternative to 24-h urine collection for assessing proteinuria. The aim of this study was to examine the correlation between the results of proteinuria assessed by the dipstick test and UPCR, and to investigate the influence of proteinuria grading with UPCR on lenvatinib dose adjustment compared to that with only the dipstick test. METHOD: Three hundred and ten urine samples from 63 patients with advanced thyroid cancer under treatment with lenvatinib, which were tested by both the dipstick test and UPCR were analyzed. Lenvatinib was withheld when there was evidence of CTCAE grade 3 proteinuria, and restarted when it resolved. The frequency of proteinuria, correlation between the results of the dipstick test and UPCR test, and the effect of dose withholding in cases with results of 3 + in the dipstick test were calculated. RESULTS: Proteinuria was seen in 56 (88.9%) patients. Of the 154 dipstick 3 + samples, only 56 (36.4%) were judged as more than 3.5 g/gCre by UPCR (grade 3 proteinuria), although none of the 1 + and only 3.7% of 2 + samples were judged as grade 3 proteinuria. We were able to prevent unnecessary lenvatinib interruption due to proteinuria in 63.6% of dipstick 3 + samples by assessment of UPCR. CONCLUSIONS: Urinalysis by combination of the dipstick test and UPCR assessment might be a better strategy for preventing unnecessary interruption of lenvatinib.


Assuntos
Antineoplásicos/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Proteinúria/induzido quimicamente , Quinolinas/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Urinálise/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Creatinina/urina , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Proteinúria/diagnóstico , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/urina
15.
Anticancer Res ; 40(4): 2089-2093, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234901

RESUMO

BACKGROUND/AIM: The outcomes of ramucirumab after lenvatinib failure for hepatocellular carcinoma (HCC) patients with alpha fetoprotein (AFP) levels of ≥400 ng/ml are unknown. PATIENTS AND METHODS: Of 12 patients treated with ramucirumab after lenvatinib failure, 10 patients were enrolled in this retrospective study. RESULTS: The disease control rate of 80% at 6 weeks and the median time to progression of 3.1 months were the same by both the Response Evaluation Criteria in Solid Tumors (RECIST) and the modified RECIST. AFP reduction was seen in 5 patients at 2 weeks and in 3 patients at 6 weeks. The incidence of grade 3 adverse events was low at 10%. The albumin-bilirubin scores within 6 weeks did not worsen. CONCLUSION: Ramucirumab might have potential therapeutic efficacy and safety in advanced HCC patients after lenvatinib failure. Further studies are needed to confirm the outcomes of ramucirumab after lenvatinib failure.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/genética , Bilirrubina/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Estudos Retrospectivos , alfa-Fetoproteínas/genética
16.
Am J Trop Med Hyg ; 103(1): 378-393, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32314694

RESUMO

Malaria volunteer infection studies (VISs) accelerate new drug and vaccine development. In the induced blood-stage malaria (IBSM) model, volunteers are inoculated with erythrocytes infected with Plasmodium falciparum. Observations of elevated liver enzymes in the IBSM model with new chemical entities (NCEs) promoted an analysis of available data. Data were reviewed from eight IBSM studies of seven different NCEs, plus two studies with the registered antimalarial piperaquine conducted between June 2013 and January 2017 at QIMR Berghofer, Brisbane, Australia. Alanine aminotransferase (ALT) was elevated (> 2.5 times the upper limit of normal [×ULN]) in 20/114 (17.5%) participants. Of these, 8.9% (10/114) had moderate increases (> 2.5-5 × ULN), noted in seven studies of six different NCEs ± piperaquine or piperaquine alone, and 8.9% (10/114) had severe elevations (> 5 × ULN), occurring in six studies of six different NCEs ± piperaquine. Aspartate aminotransferase (AST) was elevated (> 2.5 × ULN) in 11.4% (13/114) of participants, across six of the 10 studies. Bilirubin was > 2 × ULN in one participant. Published data from other VIS models, using sporozoite inoculation by systemic administration or mosquito feeding, also showed moderate/severe liver enzyme elevations. In conclusion, liver enzyme elevations in IBSM studies are most likely multifactorial and could be caused by the model conditions, that is, malaria infection/parasite density and/or effective parasite clearance, or by participant-specific risk factors, acetaminophen administration, or direct hepatotoxicity of the test drug. We make recommendations that may mitigate the risk of liver enzyme elevations in future VISs and propose measures to assist their interpretation, should they occur.


Assuntos
Alanina Transaminase/metabolismo , Antimaláricos/efeitos adversos , Aspartato Aminotransferases/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Voluntários Saudáveis , Malária Falciparum/tratamento farmacológico , Parasitemia/tratamento farmacológico , Acrilamidas/efeitos adversos , Adamantano/efeitos adversos , Adamantano/análogos & derivados , Adulto , Aminopiridinas/efeitos adversos , Aminoquinolinas/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Transfusão de Eritrócitos , Eritrócitos/parasitologia , Feminino , Compostos Ferrosos/efeitos adversos , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Humanos , Indóis/efeitos adversos , Isoquinolinas/efeitos adversos , Masculino , Metalocenos/efeitos adversos , Peróxidos/efeitos adversos , Piperazinas/efeitos adversos , Plasmodium falciparum , Primaquina/efeitos adversos , Pirimidinas/efeitos adversos , Quinolinas/efeitos adversos , Compostos de Espiro/efeitos adversos , Sulfonas/efeitos adversos , Triazóis/efeitos adversos , Adulto Jovem
17.
PLoS One ; 15(4): e0231828, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32310967

RESUMO

Lenvatinib is an approved first-line therapy for unresectable hepatocellular carcinoma (HCC), but the effect of dose modification on its efficacy is unclear. We analyzed the relationship between the relative dose intensity during the initial 4 weeks of therapy [4W-relative dose intensity (RDI)] and the efficacy of lenvatinib therapy in the real-world setting. A total of 48 consecutive patients with unresectable HCC who received lenvatinib therapy for more than 4 weeks were included. The 4W-RDI was calculated as the cumulative dose in the initial 4 weeks divided by the weight-based standard dose, and we evaluated its association with overall survival (OS) and best response by modified Response Evaluation Criteria in Solid Tumor (mRECIST). The baseline factors predicting high 4W-RDI were analyzed further. The median durations of follow-up and of therapy among the 48 participants were 7.6 and 6.6 months, respectively. The median OS was not reached. Drug interruption and/or dose reduction were necessary in 30 patients (62.5%) and the median 4W-RDI was 70% (range 22%-100%). Patients with 4W-RDI ≥70% had longer OS [hazard ratio (HR) 0.28, 95% confidential interval (CI):0.09-0.90, p = 0.03], and longer duration of lenvatinib therapy (HR 0.39, 95%CI:0.16-0.92, p = 0.03). Patients with 4W-RDI ≥70% showed higher disease control rate compared to those with 4W-RDI <70% (91.7% vs. 54.2%, p = 0.008). A baseline albumin level >3.4g/dL or ALBI score less than -2.171 were significantly associated with achieving 4W-RDI ≥70%. In conclusion, 4W-RDI of lenvatinib therapy is associated with favorable radiological response and longer OS.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/patologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Análise de Sobrevida
18.
Cancer Chemother Pharmacol ; 85(5): 907-915, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32266457

RESUMO

PURPOSE: Anlotinib is a novel oral multi-targeted receptor tyrosine kinase inhibitor, which selectively inhibits VEGFR2/3, FGFR1-4, PDGFR α/ß, c-kit, and Ret. It shows antitumor effect in patients with advanced refractory solid tumors. The detailed absorption, metabolism, and excretion pathways of anlotinib have not yet been fully investigated. METHODS: Six male patients were enrolled and divided into two groups. Group A (containing two patients) received 14.15 mg/80 µCi/subject [14C]-anlotinib hydrochloride. Group B (containing four patients) received 14.15 mg/120 µCi/subject [14C]-anlotinib hydrochloride. The blood, urine, and feces of all the six patients after orally administration of [14C]-anlotinib were collected. The absorption, metabolism, and excretion of [14C]-anlotinib were investigated, and the efficacy and safety of anlotinib were evaluated. RESULTS: In plasma, the average time to peak concentration (Tmax) of total radioactivity was 4.42 h and the average peak concentration (Cmax) of total radioactivity was 18.80 ng Eq./g. The average values of AUC0-last, AUC0-∞, and MRT0-t were 4071 h.ng Eq./g, 13,555 h.ng Eq./g, and 125 h, respectively. The average recovery of total radioactivity (TRA) in urine and feces was 62.03%, accounting for 48.52% and 13.51% in feces and urine of the total dosage, respectively. The parent drug, a carboxylic metabolite (M30), and mono-oxidation products (M46/M66) were major drug-related components in human plasma. Oxidative metabolism played the major role in drug clearance in human. The major metabolic pathways include oxidative deamination to M2, mono-oxidation to M1, and the formation of M30. Adverse events occurred in five patients and severe adverse events (SAE) occurred in one. Tumor response were evaluated as stable disease (SD) in three, partial response (PR) in one, and progressive disease (PD) in one of the patients, respectively. CONCLUSIONS: Anlotinib had a good pharmacokinetic profile with rapid absorption, long half-life, and extensive hepatic metabolism. The adverse events and efficacy were as expected.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Indóis , Neoplasias Renais/tratamento farmacológico , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinolinas , Sarcoma/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Administração Oral , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Neoplasias Colorretais/patologia , Monitoramento de Medicamentos/métodos , Humanos , Indóis/administração & dosagem , Indóis/efeitos adversos , Indóis/farmacocinética , Neoplasias Renais/patologia , Fígado/metabolismo , Masculino , Taxa de Depuração Metabólica , Desentoxicação Metabólica Fase I , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Quinolinas/farmacocinética , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/farmacocinética , Sarcoma/patologia , Distribuição Tecidual , Resultado do Tratamento
19.
Int J Hematol ; 112(1): 24-32, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32279228

RESUMO

This open-label, single-arm, phase 2 study (ClinicalTrials.gov, NCT03128411) evaluated the efficacy, safety, and pharmacokinetics of bosutinib at a starting dose of 400 mg once daily (QD) in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML). The primary endpoint was major molecular response (MMR) at Month 12 in the modified as-treated population (Philadelphia chromosome-positive [Ph+] patients with e13a2/e14a2 transcripts). Sixty Japanese patients with CP CML were treated with bosutinib; median age was 55 years (range 20-83), 60.0% were males, and all were Ph+ and had e13a2/e14a2 transcripts. After median follow-up of 16.6 months (range 11.1-21.9), 41 (68.3%) patients remained on bosutinib. The MMR rate at Month 12 was 55.0% (2-sided 90% confidence interval: 44.4-65.6). There were no on-treatment transformations to accelerated/blast phase, and no patient died on treatment or within 28 days of the last bosutinib dose. The most common treatment-emergent adverse events were diarrhea (86.7%), increased alanine aminotransferase (55.0%), and increased aspartate aminotransferase (46.7%). The primary objective of this phase 2 study was met, and there were no new safety signals for bosutinib. These data suggest bosutinib is an effective first-line treatment option for Japanese patients with newly diagnosed CP CML.


Assuntos
Compostos de Anilina/administração & dosagem , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/genética , Nitrilos/administração & dosagem , Quinolinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Compostos de Anilina/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Aspartato Aminotransferases/sangue , Diarreia , Feminino , Seguimentos , Humanos , Leucemia Mieloide de Fase Crônica/patologia , Masculino , Pessoa de Meia-Idade , Nitrilos/efeitos adversos , Cromossomo Filadélfia , Quinolinas/efeitos adversos , Transcrição Genética , Resultado do Tratamento , Adulto Jovem
20.
Tokai J Exp Clin Med ; 45(1): 18-23, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32219805

RESUMO

A 61-year-old female was diagnosed with multiple endocrine neoplasia type 2A (MEN2A), caused by a heterozygous point mutation in the RET gene (TGC to TAC at codon 634) resulting in the substitution of cytosine with leucine (C634Y). The patient had pheochromocytoma (PCC) in the left adrenal gland and medullary thyroid carcinoma (MTC) with liver metastasis. Primary hyperparathyroidism (PHP) was not evident. Family history data suggested that the RET gene mutation was inherited from the father. The PCC was removed laparoscopically, but the MTC was observed conservatively for 7 years because the status of the MTC was compatible with T1N1M1 and stage IVC; therefore, it was not curable with surgery. The MTC liver metastasis increased in size. Lenvatinib, an oral multi-tyrosine kinase inhibitor, was administered until the patient had received a total dose of 1336mg, and then administration was stopped because of nausea. The reduction rate of the MTC liver metastasis was 31%, which was considered partial response. At this point, the patient was doing well, suggesting that lenvatinib was effective in treating the MTC liver metastasis and may be one of the treatment for advanced MTC caused by C634Y mutation in the RET gene.


Assuntos
Carcinoma/etiologia , Carcinoma/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasia Endócrina Múltipla Tipo 2a/complicações , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/etiologia , Carcinoma/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/genética , Compostos de Fenilureia/efeitos adversos , Mutação Puntual , Proteínas Proto-Oncogênicas c-ret/genética , Quinolinas/efeitos adversos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia
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