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1.
Medicine (Baltimore) ; 99(41): e22707, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031343

RESUMO

RATIONALE: Anlotinib has been proved to be effective in advanced refractory non-small cell lung cancer. PATIENT CONCERNS: A 47-year-old female non-smoker was admitted due to persistent chest tightness for a month. DIAGNOSES: Epidermal growth factor receptor (EGFR) wild-type advanced primary lung adenocarcinoma without brain or bone metastasis. INTERVENTIONS: The patient failed 2 lines of pemetrexed/docetaxel plus carboplatin and third-line erlotinib. Fourth-line anlotinib was administered thereafter. OUTCOMES: The pulmonary lesions showed partial remission 5 months after anlotinib monotherapy. The patient demonstrated a progression-free survival of more than 7 months and an overall survival of >12 months. The adverse events including hypertension and fatigue were well-tolerated. LESSONS: Salvage anlotinib might be a reasonable choice in EGFR wild-type lung adenocarcinoma after failure of chemotherapy. Further well-designed trials are warranted to verify this occasional finding.


Assuntos
Adenocarcinoma/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Quinolinas/uso terapêutico , Adenocarcinoma/genética , Feminino , Genes erbB-1 , Humanos , Neoplasias Pulmonares/genética , Pessoa de Meia-Idade , Terapia de Salvação
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.
Medicine (Baltimore) ; 99(40): e22637, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019486

RESUMO

INTRODUCTION: Small cell lung cancer (SCLC) is an aggressive malignancy that progresses rapidly and easily relapses. To the best of our knowledge, advances have been minimal for decades and the first-line treatment is still platinum-etoposide and radiotherapy. However, elderly patients with severe renal failure who suffer from SCLC usually show more serious drug-related side effects. A large proportion of them cannot tolerate the standard treatment, and their prognosis is poorer compared with that of younger patients. Presently, oral etoposide capsules may be accepted as a replaceable option. We report the case of a male patient with SCLC on hemodialysis who was successfully treated with concurrent oral etoposide monotherapy and radiotherapy and achieved excellent outcomes. PATIENT'S CONCERNS: A 63-year-old man with severe renal failure was diagnosed with SCLC. PRIMARY DIAGNOSES: SCLC was diagnosed using transbronchial biopsy. INTERVENTIONS: He received concomitant single-agent oral etoposide (6 cycles) and local radiotherapy. Etoposide 100 mg once daily combined with thoracic radiation treatment (2 Gy/f, total DT: 50 Gy/25 f), was subsequently followed by prophylactic cranial irradiation plus anlotinib. OUTCOMES: The patient achieved complete response after 1 cycle and the subsequent treatment was effective without any kidney damage and other severe side effects. CONCLUSION: Though etoposide capsule is an old drug, its use should be considered in SCLC patients with renal insufficiency undergoing hemodialysis. However, treatment guidelines and research data for such patients are still lacking and further studies are needed. Although recent research focuses mainly on new drugs, some old drugs like etoposide which can bring unexpected positive effects should not be neglected.


Assuntos
Etoposídeo/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/radioterapia , Inibidores da Topoisomerase II/uso terapêutico , Administração Oral , Terapia Combinada , Irradiação Craniana/métodos , Etoposídeo/administração & dosagem , Humanos , Indóis/uso terapêutico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Quinolinas/uso terapêutico , Diálise Renal/métodos , Insuficiência Renal/terapia , Inibidores da Topoisomerase II/administração & dosagem , Resultado do Tratamento
5.
Medicine (Baltimore) ; 99(42): e22782, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080748

RESUMO

INTRODUCTION: Lenvatinib (LEN) is a novel potent multi-tyrosine kinase inhibitor, approved as first-line treatment for unresectable hepatocellular carcinoma (HCC). Considering its high objective response rate, LEN therapy could be expected to achieve downstaging of tumors and lead to conversion therapy with hepatectomy or ablation. However, the feasibility of conversion therapy after LEN treatment in unresectable HCC remains largely unknown. PATIENT CONCERNS: Here, we reported 3 cases of unresectable HCC: case 1, a 69-year-old man diagnosed with ruptured HCC; case 2, a 72-year-old woman with nonalcoholic steatohepatitis-based HCC; and case 3, a 73-year-old man with a history of alcoholic cirrhosis-based HCC. DIAGNOSIS: In all cases, cirrhosis was classified as Child-Pugh 5 and modified albumin-bilirubin grade 1 or 2a. HCC was diagnosed as Barcelona Clinic Liver Cancer (BCLC) stage B. INTERVENTIONS: In all cases, LEN was initiated after conventional-transcatheter arterial embolization enforcement, while maintaining liver function. OUTCOMES: In all cases, the main tumor size decreased after 6 months of LEN treatment and no satellite nodes were detected, indicating downstaging of HCC to BCLC stage A. Subsequently, conversion hepatectomy or ablation was performed. After successful conversion therapy, the general condition of the patients was good, without tumor recurrence during the observation period (median 10 months). LESSONS: This study demonstrated that LEN enables downstaging of HCC and thus represents a bridge to successful surgery or ablation therapy. In particular, LEN treatment may facilitate the possibility for conversion therapy of initially unresectable HCC, while maintaining the hepatic functional reserve.


Assuntos
Técnicas de Ablação , Carcinoma Hepatocelular/terapia , Hepatectomia , Neoplasias Hepáticas/terapia , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Biomarcadores/análise , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , alfa-Fetoproteínas/análise
7.
Lancet Oncol ; 21(10): 1296-1308, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32919527

RESUMO

BACKGROUND: Circulating tumour DNA (ctDNA) testing might provide a current assessment of the genomic profile of advanced cancer, without the need to repeat tumour biopsy. We aimed to assess the accuracy of ctDNA testing in advanced breast cancer and the ability of ctDNA testing to select patients for mutation-directed therapy. METHODS: We did an open-label, multicohort, phase 2a, platform trial of ctDNA testing in 18 UK hospitals. Participants were women (aged ≥18 years) with histologically confirmed advanced breast cancer and an Eastern Cooperative Oncology Group performance status 0-2. Patients had completed at least one previous line of treatment for advanced breast cancer or relapsed within 12 months of neoadjuvant or adjuvant chemotherapy. Patients were recruited into four parallel treatment cohorts matched to mutations identified in ctDNA: cohort A comprised patients with ESR1 mutations (treated with intramuscular extended-dose fulvestrant 500 mg); cohort B comprised patients with HER2 mutations (treated with oral neratinib 240 mg, and if oestrogen receptor-positive with intramuscular standard-dose fulvestrant); cohort C comprised patients with AKT1 mutations and oestrogen receptor-positive cancer (treated with oral capivasertib 400 mg plus intramuscular standard-dose fulvestrant); and cohort D comprised patients with AKT1 mutations and oestrogen receptor-negative cancer or PTEN mutation (treated with oral capivasertib 480 mg). Each cohort had a primary endpoint of confirmed objective response rate. For cohort A, 13 or more responses among 78 evaluable patients were required to infer activity and three or more among 16 were required for cohorts B, C, and D. Recruitment to all cohorts is complete and long-term follow-up is ongoing. This trial is registered with ClinicalTrials.gov, NCT03182634; the European Clinical Trials database, EudraCT2015-003735-36; and the ISRCTN registry, ISRCTN16945804. FINDINGS: Between Dec 21, 2016, and April 26, 2019, 1051 patients registered for the study, with ctDNA results available for 1034 patients. Agreement between ctDNA digital PCR and targeted sequencing was 96-99% (n=800, kappa 0·89-0·93). Sensitivity of digital PCR ctDNA testing for mutations identified in tissue sequencing was 93% (95% CI 83-98) overall and 98% (87-100) with contemporaneous biopsies. In all cohorts, combined median follow-up was 14·4 months (IQR 7·0-23·7). Cohorts B and C met or exceeded the target number of responses, with five (25% [95% CI 9-49]) of 20 patients in cohort B and four (22% [6-48]) of 18 patients in cohort C having a response. Cohorts A and D did not reach the target number of responses, with six (8% [95% CI 3-17]) of 74 in cohort A and two (11% [1-33]) of 19 patients in cohort D having a response. The most common grade 3-4 adverse events were raised gamma-glutamyltransferase (13 [16%] of 80 patients; cohort A); diarrhoea (four [25%] of 20; cohort B); fatigue (four [22%] of 18; cohort C); and rash (five [26%] of 19; cohort D). 17 serious adverse reactions occurred in 11 patients, and there was one treatment-related death caused by grade 4 dyspnoea (in cohort C). INTERPRETATION: ctDNA testing offers accurate, rapid genotyping that enables the selection of mutation-directed therapies for patients with breast cancer, with sufficient clinical validity for adoption into routine clinical practice. Our results demonstrate clinically relevant activity of targeted therapies against rare HER2 and AKT1 mutations, confirming these mutations could be targetable for breast cancer treatment. FUNDING: Cancer Research UK, AstraZeneca, and Puma Biotechnology.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , DNA Tumoral Circulante/sangue , Terapia de Alvo Molecular , Adulto , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor alfa de Estrogênio/genética , Feminino , Fulvestranto/uso terapêutico , Genótipo , Humanos , Pessoa de Meia-Idade , Mutação , PTEN Fosfo-Hidrolase/genética , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Quinolinas/uso terapêutico , Receptor ErbB-2/genética , Receptores Estrogênicos/antagonistas & inibidores , Receptores Estrogênicos/genética , Receptores Estrogênicos/metabolismo , Resultado do Tratamento
8.
Artigo em Inglês | MEDLINE | ID: mdl-32872631

RESUMO

(1) Background: Statin is the mainstay of treatment for the primary prevention of atherosclerotic cardiocerebrovascular diseases (CCVDs) in adults with hypercholesterolemia. This study aims to investigate the differences in effect on primary composite outcomes (CCVDs and CCVD-related deaths) among five statins in hypercholesterolemic individuals. (2) Methods: This retrospective study is based on the Korean National Health Insurance Service-National Health Screening Cohort. Participants, aged 40 to 69 years at baseline, were categorized into five statin-treated groups (pitavastatin, atorvastatin, rosuvastatin, simvastatin, and pravastatin) and two untreated groups (untreated hypercholesterolemia and no hypercholesterolemia). (3) Results: A total of 161,583 individuals was included. The median follow-up period was 8.2 years. Compared with the pitavastatin group, the hazard ratios (HRs; 95% confidence intervals (CIs)) for CCVDs and CCVD-related deaths of the atorvastatin, rosuvastatin, simvastatin, pravastatin, untreated hypercholesterolemia, and no-hypercholesterolemia groups were 0.969 (0.567-1.657), 0.988 (0.533-1.832), 0.862 (0.490-1.518), 0.906 (0.326-2.515), 2.665 (1.556-4.562), and 0.656 (0.388-1.110), respectively, in men and 1.124 (0.632-1.999), 1.119 (0.582-2.152), 1.324 (0.730-2.400), 1.023 (0.330-3.171), 2.650 (1.476-4.758), and 0.921 (0.522-1.625), respectively, in women, after being fully adjusted. (4) Conclusions: No significant differences among the five statins were observed, but there was an increased risk in untreated hypercholesterolemic individuals, for CCVDs and CCVDs-related deaths in individuals with hypercholesterolemia of either sex.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Transtornos Cerebrovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Adulto , Idoso , Atorvastatina/uso terapêutico , Doenças Cardiovasculares/mortalidade , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/mortalidade , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Hipercolesterolemia/etiologia , Masculino , Pessoa de Meia-Idade , Pravastatina/uso terapêutico , Prevenção Primária , Pirróis , Quinolinas/uso terapêutico , Estudos Retrospectivos , Rosuvastatina Cálcica/uso terapêutico , Sinvastatina/uso terapêutico
9.
Oncology ; 98(11): 779-786, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877911

RESUMO

BACKGROUND AND AIMS: Lenvatinib is an oral anticancer drug for patients with unresectable advanced hepatocellular carcinoma (HCC). We evaluated whether a reduction in tumor stain at 2 weeks after lenvatinib treatment in patients with unresectable HCC is a predictor of early treatment efficacy at 12 weeks. PATIENTS AND METHODS: Of the 23 patients who initiated lenvatinib treatment between April 2018 and January 2019, treatment efficacy was measured in 15 patients for more than 12 weeks after treatment. Changes in tumor stain, tumor size on contrast-enhanced computed tomography (CT), and serum levels of tumor markers were evaluated 2 weeks after lenvatinib treatment. Therapeutic efficacy was assessed by tumor stain and tumor size by contrast-enhanced CT within the first 12 weeks, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. RESULTS: At 12 weeks, efficacy evaluation of 15 patients revealed that 11 of them experienced partial responses, for a response rate of 73.3%. In the first 2 weeks, 13 patients (86.7%) experienced a decreased tumor stain, including 10 responders (90.9%) and 3 non-responders (75.0%). All patients in the non-responder group had required a lenvatinib dose reduction due to adverse events within 12 weeks. On contrast-enhanced CT, the change rate of tumor stain to HCC at 2 weeks after treatment was <0.8 among 10 responders (90.9%) and 1 non-responder (25.0%; p = 0.033). No significant differences between responders and non-responders were observed with regard to most characteristics at baseline and at 2 weeks after treatment initiation. However, significant differences were observed between groups in the presence or absence of a dose suspension period, the presence or absence of lenvatinib dose reduction from the maximum value during the first 2 weeks, and decreased tumor stain at 2 weeks after treatment initiation. CONCLUSION: Reduction in tumor stain at 2 weeks after lenvatinib treatment may be an early biomarker of efficacy at 12 weeks in patients with unresectable HCC.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Precursores de Proteínas/sangue , Protrombina , Critérios de Avaliação de Resposta em Tumores Sólidos , Coloração e Rotulagem/métodos , Tomografia Computadorizada por Raios X , alfa-Fetoproteínas/metabolismo
10.
Oncology ; 98(11): 787-797, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32882687

RESUMO

BACKGROUND: Although a strong antitumor effect of lenvatinib (LEN) has been noted for patients with unresectable hepatocellular carcinoma (HCC), there are still no reports on the prognosis for patients with disease progression after first-line LEN therapy. METHODS: Patients (n = 141) with unresectable HCC, Child-Pugh class A liver function, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 who were treated with LEN from March 2018 to December 2019 were enrolled. RESULTS: One hundred and five patients were treated with LEN as first-line therapy, 53 of whom had progressive disease (PD) at the radiological evaluation. Among the 53 patients with PD, there were 27 candidates for second-line therapy, who had Child-Pugh class A liver function and an ECOG-PS of 0 or 1 at progression. After progression on first-line LEN, 28 patients were treated with a molecular targeted agent (MTA) as second-line therapy (sorafenib: n = 26; ramucirumab: n = 2). Multivariate analysis identified modified albumin-bilirubin grade 1 or 2a at LEN initiation (odds ratio 5.18, 95% confidence interval [CI] 1.465-18.31, p = 0.011) as a significant and independent factor for candidates. The median post-progression survival after PD on first-line LEN was 8.3 months. Cox hazard multivariate analysis showed that a low alpha-fetoprotein level (<400 ng/mL; hazard ratio [HR] 0.297, 95% CI 0.099-0.886, p = 0.003), a relative tumor volume <50% at the time of progression (HR 0.204, 95% CI 0.07-0.592, p = 0.03), and switching to MTAs as second-line treatment after LEN (HR 0.299, 95% CI 0.12-0.746, p = 0.01) were significant prognostic factors. CONCLUSION: Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Sorafenibe/uso terapêutico , Taxa de Sobrevida
11.
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
12.
Medicine (Baltimore) ; 99(36): e22128, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899099

RESUMO

RATIONALE: Brain metastasis (BM) is a serious complication in non-small cell lung cancer (NSCLC) patients. Pemetrexed is one of the preferred agents in nonsquamous NSCLC with BM; however, the traditional chemotherapy demonstrated limited efficacy partly due to drug resistance and the blood-brain barrier. PATIENT CONCERNS: A 52-year-old male non-smoker was admitted for irritating cough, chest distress, and back pain. DIAGNOSES: Epidermal growth factor receptor wild-type, anaplastic lymphoma kinase-negative primary lung adenocarcinoma with an asymptomatic solitary BM (cTxNxM1b, IVA). INTERVENTIONS: Pemetrexed (500 mg/m of body surface area) and carboplatin (area under the curve of 5) were firstly administered every 3 weeks for 3 cycles, followed by pemetrexed/carboplatin plus anlotinib (12 mg daily; 2 weeks on and 1 week off) for another 3 cycles. Then maintenance anlotinib monotherapy was continued for a year, without unacceptable adverse events. OUTCOMES: The BM was slightly enlarged after 3 cycles of pemetrexed/carboplatin; however, a complete remission was achieved after the combination therapy. His intracranial progression-free survival was more than 2 years. LESSONS: Pemetrexed/carboplatin plus anlotinib could be considered for the treatment of epidermal growth factor receptor wild-type, anaplastic lymphoma kinase-negative lung adenocarcinoma with BM. Further well-designed trials are warranted to verify this occasional finding.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Quinase do Linfoma Anaplásico/metabolismo , Carboplatina/uso terapêutico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pemetrexede/uso terapêutico , Quinolinas/uso terapêutico
13.
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
14.
Z Gastroenterol ; 58(8): 773-777, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32785913

RESUMO

In recent years, immune checkpoint inhibitors (ICIs) were successfully introduced to cancer therapy, and these drugs have already become essential for the treatment of various noncurable tumors. However, monotherapy in advanced hepatocellular carcinoma (aHCC) failed to show statistically significant improvement.Recently, the combination of atezolizumab and bevacizumab demonstrated efficacy of combining ICI and VEGF inhibition, further substantiating previous data on synergistic mechanisms among respective substance classes.As TKI treatment is currently standard of care for aHCC, and ICIs are approved by the FDA and available in many areas of the world, numerous patients may have been treated with monotherapy of those drugs. However, it remains unclear if failure to monotherapy has an impact on combination therapy. We therefore report a patient well responding to combination therapy despite previous failures to TKI and ICI monotherapy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Quimioterapia Combinada , Humanos , Resultado do Tratamento
15.
Am J Cardiol ; 132: 15-21, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32773226

RESUMO

Lipid-lowering therapy is necessary to reduce cardiovascular event rates in patients with ST-segment elevation myocardial infarction (STEMI). This study aimed to evaluate the effect of intensive lipid-lowering therapy, which comprised pitavastatin and ezetimibe, on patients with STEMI. We therefore undertook a post hoc subanalysis of the HIJ-PROPER study's data that examined the clinical outcomes of the patients with dyslipidemia and STEMI (n = 880) who received pitavastatin and ezetimibe therapy (intensive lipid-lowering therapy group) or pitavastatin monotherapy (standard lipid-lowering therapy group), and we evaluated their cardiovascular events. The primary end point was a composite of all-cause death, nonfatal myocardial infarction, nonfatal stroke, unstable angina, and ischemia-driven revascularization. During the median 3.4-year follow-up period, the cumulative rates of the primary end point were 31.9% and 39.7% in the intensive lipid-lowering therapy and standard lipid-lowering therapy groups, respectively (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.62 to 0.97; p = 0.02). Compared with the standard lipid-lowering therapy group, the intensive lipid-lowering therapy group had significantly lower all-cause death (6.9% vs 3.2%; HR, 0.45; 95% CI, 0.23 to 1.84; p = 0.01) and nonfatal stroke (2.9% vs 1.6%; HR, 0.77; 95% CI, 0.62 to 0.97; p = 0.02) rates. Patients with pitavastatin and ezetimibe therapy, as compared with pitavastatin monotherapy, had a lower cardiovascular event in STEMI patients. In conclusion, adding ezetimibe to statin therapy may be beneficial for patients with dyslipidemia and STEMI.


Assuntos
Ezetimiba/uso terapêutico , Quinolinas/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Anticolesterolemiantes/uso terapêutico , Biomarcadores/sangue , LDL-Colesterol/sangue , Dinamarca/epidemiologia , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Método Simples-Cego , Taxa de Sobrevida/tendências , Resultado do Tratamento
16.
PLoS One ; 15(8): e0238207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32841270

RESUMO

BACKGROUND: Although infrequent, distant metastasis from differentiated thyroid cancer is the main cause of mortality in patients and mostly involves the lung, bone, and brain. Distant metastases to other sites in differentiated thyroid cancer patients are rare, thus, the clinical course of unusual metastases has not been adequately researched. In the present study, the clinico-pathological findings and treatment outcomes of unusual metastases in differentiated thyroid cancer patients in Korea were evaluated. PATIENTS AND METHODS: We retrospectively reviewed the medical records of differentiated thyroid cancer patients with unusual metastases in four Korean tertiary hospitals (Chonnam National University Hwasun Hospital, Asan Medical Center, Busan National University Hospital, Severance Hospital). Unusual metastases were diagnosed using (1) cytology or histology and/or (2) imaging studies including fluorodeoxyglucose F 18 positron emission tomography/computed tomography and/or iodine 131 whole body scans with simultaneously elevated serum levels of thyroglobulin. The pathological findings of primary thyroid cancer, diagnostic method for unusual metastases, and treatment responses of unusual metastases were examined. RESULTS: In all, 25 unusual metastatic foci of 19 patients were analyzed; 13 patients (68.4%) had papillary thyroid carcinoma including 4 follicular variant papillary thyroid carcinomas. The median time interval between the first diagnosis of primary thyroid cancer and unusual metastases diagnosis was 110 months (11.0-138.0 months). Only 4 patients (21.1%) had synchronous unusual metastases and 6 patients (31.6%) were symptomatic. Unusual metastases included 19 metastases to solid organs (6 to kidney, 5 to liver, 4 to pancreas, 3 to adrenal gland, and 1 to ovary) and 6 to the skin and muscles. Unusual metastases were pathologically proven in 10 patients (52.6%) and 11 of 16 patients (68.8%) who received iodine 131 whole body scans had radioiodine-refractory differentiated thyroid cancer. Among 5 patients treated with tyrosine kinase inhibitors, 4 treated with lenvatinib showed stable disease or a partial response at the first treatment response. Six patients (31.6%) died due to disease progression during the median 20.0-month follow-up period (11.0-55.0 months). CONCLUSION: Unusual metastases from differentiated thyroid cancer are thought to be underestimated due to disease rarity and their metachronous nature with other distant metastases. The most of unusual metastases in differentiated thyroid cancer patients are existed with usual distant metastasis and clinical outcomes of those could not be significantly different from the prognosis of usual distant metastasis.


Assuntos
Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Carcinoma Papilar/secundário , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/patologia , Metástase Neoplásica/terapia , Especificidade de Órgãos , Compostos de Fenilureia/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , República da Coreia , Estudos Retrospectivos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/terapia , Fatores de Tempo , Imagem Corporal Total
17.
PLoS One ; 15(8): e0237370, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857769

RESUMO

BACKGROUND: Copper (Cu) and zinc (Zn) are essential nutrients and cofactors of enzymatic reactions with their binding partner. Metallothionein (MT) plays an important role in protecting against heavy metals and oxidative injury, however it may also portend drug resistance and a worse prognosis for hepatocellular carcinoma (HCC) patients. The aim of this study was to determine the amount of Cu, Zn, Cu/Zn and MT in evaluating a group of patients with HCC, including those treated with lenvatinib. METHODS: We enrolled 175 patients with HCC (139 men, 36 women; mean age 71.1 years; hepatitis C virus n = 85, hepatitis B virus n = 19, hepatitis C virus and hepatitis B virus n = 2, non-alcoholic steatohepatitis n = 39, alcohol n = 25, others n = 5; Child-Pugh A n = 141, Child-Pugh B n = 30, Child-Pugh C n = 4; Barcelona clinic liver cancer (BCLC) stage 0 n = 38, stage A n = 56, stage B n = 39, stage C n = 38, stage D n = 4). We evaluated the associations between Cu, Zn and MT. The study outcome was liver cancer-specific survival. Moreover, we treated 12 HCC patients with lenvatinib and investigated the changes in MT during lenvatinib therapy. RESULTS: The serum level of Cu was positively correlated with alanine aminotransferase and the BCLC stage. The serum level of Zn decreased concordant with liver disease progression. Patients with a Cu/Zn ratio≥0.999 had significantly improved rates of survival when compared to patients with a Cu/Zn ratio<0.999 (45.3 vs. 30.1 months, p<0.001). MT was significantly correlated with the Cu/Zn ratio and increased after the administration of lenvatinib. Using multivariate Cox regression analyses, it was determined that the Cu/Zn ratio (hazard ratio [HR]: 1.442, p = 0.008), alpha-fetoprotein (HR: 1.000, p<0.001) and BCLC stage (HR: 2.087, p<0.001) were independent predictors of survival. CONCLUSIONS: The Cu/Zn ratio could serve as a useful predictive marker for survival in cases of HCC. MT levels increased in HCC patients receiving lenvatinib therapy, and maybe a predictor of reduced survival.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Cobre/sangue , Neoplasias Hepáticas/sangue , Metalotioneína/sangue , Zinco/sangue , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico
18.
Am J Trop Med Hyg ; 103(2_Suppl): 28-36, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618242

RESUMO

From 2014 to 2016, a community-randomized controlled trial in Southern Province, Zambia, compared mass drug administration (MDA) and focal MDA (fMDA) with the standard of care. Acceptability of the intervention was assessed quantitatively using closed-ended and Likert scale-based questions posed during three household surveys conducted from April to May in 2014, 2015, and 2016 in 40 health catchments that implemented MDA and fMDA and 20 catchments that served as trial controls. In 2014 and 2015, 47 households per catchment were selected, targeting 1,880 households in MDA and fMDA trial arms; in 2016, 55 households per catchment were selected for a target of 2,200 households in MDA and fMDA trial arms. Concurrently, 27 focus group discussions and 23 in-depth interviews with 248 participants were conducted on reasons for testing and treatment refusal, reasons for nonadherence, and community perception of the MDA campaign. Results demonstrated that the MDA campaign was highly accepted with more than 99% of respondents stating that they would take treatment if positive for malaria. High acceptability at baseline could be associated with test-and-treat campaigns recently conducted in the study area. There was a large increase in the acceptability of prophylactic treatment if negative for malaria from the baseline to follow-up survey for adults and children, from 62% to 96% for each. This likely resulted from an intensive community-wide sensitization program that occurred before the first treatment round at each household during community health worker visits.


Assuntos
Artemisininas/administração & dosagem , Atitude Frente a Saúde , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos , Aceitação pelo Paciente de Cuidados de Saúde , Quinolinas/administração & dosagem , Adulto , Artemisininas/uso terapêutico , Erradicação de Doenças/métodos , Quimioterapia Combinada , Feminino , Grupos Focais , Humanos , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Quinolinas/uso terapêutico , Zâmbia/epidemiologia
19.
Am J Trop Med Hyg ; 103(2_Suppl): 54-65, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618245

RESUMO

Rigorous evidence of effectiveness is needed to determine where and when to apply mass drug administration (MDA) or focal MDA (fMDA) as part of a malaria elimination strategy. The Zambia National Malaria Elimination Centre recently completed a community-randomized controlled trial in Southern Province to evaluate MDA and fMDA for transmission reduction. To assess the role of MDA and fMDA on infection incidence, we enrolled a longitudinal cohort for an 18-month period of data collection including monthly malaria parasite infection detection based on polymerase chain reaction and compared time to first infection and cumulative infection incidence outcomes across study arms using Cox proportional hazards and negative binomial models. A total of 2,026 individuals from 733 households were enrolled and completed sufficient follow-up for inclusion in analysis. Infection incidence declined dramatically across all study arms during the period of study, and MDA was associated with reduced risk of first infection (hazards ratio: 0.36; 95% CI: 0.16-0.80) and cumulative infection incidence during the first rainy season (first 5 months of follow-up) (incidence rate ratio: 0.34; 95% CI: 0.12-0.95). No significant effect was found for fMDA or for either arm over the full study period. Polymerase chain reaction infection status at baseline was strongly associated with follow-up infection. The short-term effects of MDA suggest it may be an impactful accelerator of transmission reduction in areas with high coverage of case management and vector control and should be considered as part of a malaria elimination strategy.


Assuntos
Malária Falciparum/epidemiologia , Administração Massiva de Medicamentos , Adolescente , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Criança , Pré-Escolar , Erradicação de Doenças/métodos , Erradicação de Doenças/estatística & dados numéricos , Quimioterapia Combinada , Características da Família , Feminino , Humanos , Incidência , Estudos Longitudinais , Malária Falciparum/tratamento farmacológico , Malária Falciparum/prevenção & controle , Masculino , Administração Massiva de Medicamentos/métodos , Administração Massiva de Medicamentos/estatística & dados numéricos , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Adulto Jovem , Zâmbia/epidemiologia
20.
Am J Trop Med Hyg ; 103(2_Suppl): 7-18, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618247

RESUMO

Over the past decade, Zambia has made substantial progress against malaria and has recently set the ambitious goal of eliminating by 2021. In the context of very high vector control and improved access to malaria diagnosis and treatment in Southern Province, we implemented a community-randomized controlled trial to assess the impact of four rounds of community-wide mass drug administration (MDA) and household-level MDA (focal MDA) with dihydroartemisinin-piperaquine (DHAP) implemented between December 2014 and February 2016. The mass treatment campaigns achieved relatively good household coverage (63-79%), were widely accepted by the community (ranging from 87% to 94%), and achieved very high adherence to the DHAP regimen (81-96%). Significant declines in all malaria study end points were observed, irrespective of the exposure group, with the overall parasite prevalence during the peak transmission season declining by 87.2% from 31.3% at baseline to 4.0% in 2016 at the end of the trial. Children in areas of lower transmission (< 10% prevalence at baseline) that received four MDA rounds had a 72% (95% CI = 12-91%) reduction in malaria parasite prevalence as compared with those with the standard of care without any mass treatment. Mass drug administration consistently had the largest short-term effect size across study end points in areas of lower transmission following the first two MDA rounds. In the context of achieving very high vector control coverage and improved access to diagnosis and treatment for malaria, our results suggest that MDA should be considered for implementation in African settings for rapidly reducing malaria outcomes in lower transmission settings.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária Falciparum/prevenção & controle , Administração Massiva de Medicamentos/métodos , Quinolinas/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Erradicação de Doenças/métodos , Quimioterapia Combinada , Humanos , Incidência , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Avaliação de Programas e Projetos de Saúde , Quinolinas/uso terapêutico , Zâmbia/epidemiologia
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