Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45.053
Filtrar
1.
Bratisl Lek Listy ; 122(8): 531-537, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34282617

RESUMO

OBJECTIVES: The aim of this study was to assess cardiotoxicity and potential adverse effects related to lipid metabolism during treatment with tyrosine kinase inhibitors (TKIs) imatinib and nilotinib in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: Eighty-two consecutive patients with CML, who received nilotinib and/or imatinib in a single haemato-oncological Slovak center between years 2002-2018 were evaluated in a retrospective study. The mean age was 55.8 years (range 22-77 years). Median of follow-up was 61.3 months. RESULTS: A significantly higher incidence of dyslipidemia, significantly higher levels of potential risk markers of cardiovascular disease small dense LDL cholesterol (sdLDL-CH) and a significant increase in total cholesterol were found in the patients during treatment with nilotinib in comparison to imatinib. Dyslipidemia led to drug therapy in 22 % of the patients in the nilotinib group. Fourteen percent of the patients in the nilotinib group had one or more cardiovascular events, including peripheral artery disease (10 %), myocardial infarction (4 %) and stroke (4 %). CONCLUSION: A higher risk of cardiovascular events and atherogenic dyslipidemia were associated with nilotinib therapy. Patients treated with TKI, especially nilotinib, require an early modification of cardiovascular risk factors and a careful cardiologic surveillance so that antileukemic therapy with this highly effective agent could continue (Tab. 4, Fig. 3, Ref. 32). Text in PDF www.elis.sk Keywords: tyrosine kinase inhibitors, cardiovascular events, dyslipidemia, small dense LDL-cholesterol, nilotinib, imatinib.


Assuntos
Antineoplásicos , Doenças Cardiovasculares , Leucemia Mielogênica Crônica BCR-ABL Positiva , Adulto , Idoso , Antineoplásicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Humanos , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Lipídeos , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas , Estudos Retrospectivos , Adulto Jovem
2.
Emerg Med Clin North Am ; 39(3): 555-571, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34215402

RESUMO

Pediatric hematologic and oncologic emergencies are in 3 major categories: complications of hematologic disorders, emergencies associated with the new onset of cancers, and treatment-associated oncologic emergencies. The overall number of these patients remains low; however, the mortality associated with these diseases remains high despite significant advances in management. This article presents a review of the most commonly encountered pediatric hematologic and oncologic complications that emergency physicians and providers need to know.


Assuntos
Anemia Falciforme , Antineoplásicos/efeitos adversos , Neoplasias , Púrpura Trombocitopênica Idiopática , Anemia Falciforme/diagnóstico , Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Criança , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Humanos , Incidência , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapia , Medicina de Emergência Pediátrica , Prevalência , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/terapia
3.
Gan To Kagaku Ryoho ; 48(7): 959-962, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34267036

RESUMO

An 86-year-old man was referred to our hospital with pulmonary tuberculosis developed during postoperative chemotherapy for gastric cancer. We initiated treatment with an anti-tuberculosis drug. Following confirmation of the effectiveness of this regimen, we combined the treatment with anti-cancer drugs. Tuberculosis treatment was completed without any drug interactions or serious side effects due to multidrug administration. For cancer patients who developed tuberculosis, combination treatment requires careful observation; however, it is a treatment option that can control both diseases.


Assuntos
Antineoplásicos , Neoplasias Gástricas , Tuberculose Pulmonar , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antituberculosos/efeitos adversos , Humanos , Masculino , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Tuberculose Pulmonar/tratamento farmacológico
4.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206364

RESUMO

Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 µg/µL) injection at the same time point; and (ii) UCMSC exosome (1.2 µg/µL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin-injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity-induced hearing loss by promoting tissue remodeling and repair.


Assuntos
Doenças Cocleares/etiologia , Doenças Cocleares/terapia , Exossomos/metabolismo , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Células Ciliadas Auditivas Externas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical/citologia , Animais , Antineoplásicos/efeitos adversos , Terapia Biológica , Biomarcadores , Cisplatino/efeitos adversos , Doenças Cocleares/patologia , Modelos Animais de Doenças , Exossomos/transplante , Células Ciliadas Auditivas Externas/patologia , Perda Auditiva/etiologia , Perda Auditiva/metabolismo , Perda Auditiva/terapia , Imunofenotipagem , Camundongos , MicroRNAs/genética , Proteômica/métodos , Resultado do Tratamento
5.
Int J Mol Sci ; 22(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208601

RESUMO

Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-ß1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.


Assuntos
Metabolismo dos Carboidratos , Neoplasias Colorretais/metabolismo , Glucose/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Transdução de Sinais , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Neoplasias Colorretais/complicações , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/terapia , Suscetibilidade a Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Fator de Crescimento Insulin-Like I/genética , Doenças Metabólicas/etiologia , Doenças Metabólicas/prevenção & controle , Fatores de Risco
6.
Nutrients ; 13(6)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198618

RESUMO

Chrysin belongs to the group of natural polyphenols. It can be found, among others, in honey, propolis and fruits and has a wide range of biological activities, including the prevention of oxidative stress, inflammation, neurodegeneration and carcinogenesis. Being a part of the human diet, chrysin is considered to be a promising compound to be used in the prevention of many diseases, including cancers, diabetes and neurodegenerative diseases such as Alzheimer's or Parkinson's. Nevertheless, due to the low solubility of chrysin in water and under physiological conditions, its bioavailability is low. For this reason, attempts at its functionalization have been undertaken, aiming to increase its absorption and thus augment its in vivo therapeutic efficacy. The aim of this review is to summarize the most recent research on chrysin, including its sources, metabolism, pro-health effects and the effects of its functionalization on biological activity and pharmacological efficacy, evaluated both in vitro and in vivo.


Assuntos
Flavonoides , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Disponibilidade Biológica , Portadores de Fármacos , Oftalmopatias/tratamento farmacológico , Flavonoides/administração & dosagem , Flavonoides/química , Flavonoides/metabolismo , Flavonoides/farmacologia , Humanos , Inflamação/tratamento farmacológico , Fígado/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Neuroproteção , Polifenóis , Dermatopatias/tratamento farmacológico
8.
Gan To Kagaku Ryoho ; 48(6): 849-852, 2021 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-34139738

RESUMO

We encountered 3 cases suggesting that coadministration of herbal medicines may reduce the side effects of anticancer drugs and reinforce cancer growth control. In 2 cases, on observing anticancer drug resistance, it was possible to regain control of cancer growth by coadministering herbal medicines. In the remaining 1 case, thrombocytopenia was observed during chemotherapy, which could be avoided by coadministering a herbal medicine. If the expected effect is not obtained even after herbal medicine administration, it is important to consider additional herbal medications.


Assuntos
Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicamentos de Ervas Chinesas , Neoplasias , Antineoplásicos/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Medicina Herbária , Humanos , Neoplasias/tratamento farmacológico
9.
Artigo em Inglês | MEDLINE | ID: mdl-34073174

RESUMO

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of neurotoxic anticancer drugs that may affect quality of life (QoL). Purpose: The purposes of this study were to: assess the levels of CIPN, anxiety, depression, CIPN-related QoL, and general QoL; and identify the factors related to CIPN-related QoL and general QoL in patients with advanced lung cancer (LC) receiving platinum-based chemotherapy. This cross-sectional study examined patients with advanced LC who received platinum-based chemotherapy from the thoracic oncology inpatient wards of a medical center in northern Taiwan. Structured questionnaires were used to measure patients' CIPN (European Organization for Research and Treatment of Cancer quality of life questionnaire-chemotherapy-induced peripheral neuropathy 20), anxiety (Hospital Anxiety and Depression Scale Depression Scale [HADS]), depression (HADS), CIPN-related QoL (Functional Assessment of Cancer Therapy /Gynecologic Oncology Group-Neurotoxicity subscale [FACT/GOG-Ntx]), and general QoL (Functional Assessment of Cancer Therapy-General Input [FACT-G]). Of 93 patients with advanced LC, 53.8% reported CIPN-sensory impairment and 47.3% reported CIPN-motor impairment. The most common CIPN symptoms were difficulty getting or maintaining an erection (only for men > 65 years) and difficulty in climbing stairs or getting up out of a chair. Poor CIPN-related QoL (FACT/GOG-Ntx) was associated with more CIPN-sensory and more CIPN-motor impairment. Poor general QoL (FACT-G) was associated with a higher level of depression, a higher level of anxiety, and receipt of more chemotherapy cycles. More than half of LC patients report impairment related to CIPN, calling for holistic treatment to improve QoL.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Doenças do Sistema Nervoso Periférico , Antineoplásicos/efeitos adversos , Estudos Transversais , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/epidemiologia , Platina , Qualidade de Vida , Taiwan/epidemiologia
10.
Gen Dent ; 69(4): 70-74, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34185672

RESUMO

The objective of this study was to investigate the relationship between antineoplastic treatments and oral complications in patients with head and neck cancer. Medical records from 400 patients treated at a cancer center were analyzed. Univariable analysis was initially performed to verify the association between the variables and the presence of oral complications. Multivariable analysis was performed using multiple linear regression to assess the association between the type of treatment performed and the presence and types of oral complications. The medical records of 290 patients included information about the presence or absence of oral complications of therapy, and 199 of these patients experienced oral complications. An average of 1 oral complication per patient was found; 104 patients experienced 1 complication, 74 patients experienced 2 complications, and 21 patients experienced 3 or 4 complications. Oral complications were correlated with tobacco use (P = 0.01), alcohol use (P = 0.006), radiotherapy (P = 0.000), and chemotherapy (P = 0.028). The association between oral complications and radiotherapy was greater than the association between oral complications and chemotherapy, but the risk increased when both therapies were performed (odds ratio [OR] = 4.41; P = 0.004). Mucositis was associated with both radiotherapy and chemotherapy, and the incidence increased when both types of treatment were combined (OR = 5.28; P = 0.001). Oral complications of antineoplastic therapy are related to lifestyle habits and treatment modalities. Clinicians should educate patients with head and neck cancer about the role of lifestyle habits in possible adverse treatment effects and consider a more careful approach to follow-up care of patients who are undergoing both radiotherapy and chemotherapy.


Assuntos
Antineoplásicos , Neoplasias de Cabeça e Pescoço , Estomatite , Antineoplásicos/efeitos adversos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Probabilidade
11.
J Stroke Cerebrovasc Dis ; 30(8): 105883, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34090174

RESUMO

Nilotinib, a BCR-ABL tyrosine kinase inhibitor (TKI), has been associated with vascular events and accelerated arterial stenosis, presumably of atherosclerotic etiology. Studies of nilotinib-associated atherosclerosis are mainly associated with progressive peripheral artery occlusive disease (PAOD), and only a few cases of coronary artery disease (CAD), and cerebrovascular disease (CVD) have been reported. The mechanisms by which nilotinib promotes atherosclerosis are poorly understood but endothelial and perivascular factors, mast cell depletion, and metabolic factors such as promotion of dyslipidemia and impaired glucose metabolism are thought to play a role. We present a case of a patient with chronic myelogenous leukemia (CML) treated with nilotinib who developed intracranial atherosclerosis leading to acute onset of stroke. Our patient had no cardiovascular risk factors prior to treatment with nilotinib and developed accelerated atheromatous cerebrovascular disease with severe left middle cerebral artery (MCA) stenosis. These findings suggest that nilotinib may be associated with the development of intracranial atherosclerotic disease (ICAD) independently of any preexisting vascular risk factors leading to acute stroke. Clinicians should have increased awareness of the association between nilotinib and the development of progressive atheromatous disease and vascular adverse events including PAOD, CAD, and CVD. In certain patients, these events can be severe and life threatening. Thus, screening for vascular risk factors including CVD prior to starting nilotinib and close follow up during treatment is crucial.


Assuntos
Antineoplásicos/efeitos adversos , Infarto da Artéria Cerebral Média/etiologia , Arteriosclerose Intracraniana/induzido quimicamente , AVC Isquêmico/etiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Estado Funcional , Humanos , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/terapia , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/terapia , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/terapia , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Fatores de Risco , Resultado do Tratamento
12.
Rev Prat ; 71(2): 193-197, 2021 Feb.
Artigo em Francês | MEDLINE | ID: mdl-34160983

RESUMO

"Renal toxicity of antineoplasic agents Renal toxicity of antineoplasic agents is a common complication faced by oncologists and nephrologists whose incidence depends on therapeutic classes used and patient's comorbidities. Nephrotoxicity is variable, according to mecanisms, chronology and potential reversibility. Besides acute kidney injury and/or chronic kidney disease, clinical features include several urinary abnormalities (mainly proteinuria). The onset of renal toxicity may directly compromise vital prognosis and may lead to the interruption of medications affecting cancer-specific mortality. Nephrotoxicity prevention (when feasible) and rapid diagnosis are essential to optimize cancer-patient medical care."


Assuntos
Injúria Renal Aguda , Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias , Insuficiência Renal Crônica , Injúria Renal Aguda/induzido quimicamente , Antineoplásicos/efeitos adversos , Humanos , Neoplasias/tratamento farmacológico
13.
Rev Prat ; 71(2): 198-205, 2021 Feb.
Artigo em Francês | MEDLINE | ID: mdl-34160984

RESUMO

"Targeted therapies and pathophysiological mechanisms of proteinuria Targeted therapy represents a promising therapeutic approach for patients with diverse cancers and has enabled significant development in medical oncology. This new class of anticancer drugs includes antibodies, fusion-proteins and receptor tyrosine kinase inhibitors among others. Depending on their molecular targeting, side effects can affect multiple organs, especially the kidney. Antiangiogenic agents inhibit the VEGF/VEGFR pathway resulting in reduction of nitric oxide production and alteration of podocytes function, which causes hypertension and proteinuria. EGFR inhibitors are responsible of electrolytic disorders. Hereby, we synthetized the current knowledge on renal toxicities on main molecular targeted therapies. Toxicities management is mainly based on clinical and biological monitoring, which can lead to drug withdrawing or dose adaptation."


Assuntos
Antineoplásicos , Insuficiência Renal , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/efeitos adversos , Humanos , Rim , Oncologia , Terapia de Alvo Molecular/efeitos adversos
14.
Medicine (Baltimore) ; 100(22): e26245, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087912

RESUMO

BACKGROUND: Breast cancer was the second cause of cancer death and approximately accounted for 30% of all newly diagnosed cancer in American women. Adjuvant chemotherapy is the preferred treatment approach for breast patients. Kanglaite injection (KI) was commonly used as adjuvant chemotherapy combined with chemotherapy for women breast cancer which could increase chemotherapy efficacy and alleviate chemotherapy drugs induced adverse events, however, the efficacy and safety for KI combined western medicine remains controversial. Thus, we conducted this protocol of systematic review and meta-analysis to estimate the efficacy and safety of KI combined with western medicine for women breast cancer. METHODS: This study will search electronic database included English medicals databases and Chinese databased up to May 2021. The main outcomes of this study include clinical efficacy rate. Adverse reaction rate, Karnofsky Performance Status and immune function were defined as the secondary outcomes. RESULTS: This protocol study will comprehensively evaluate the efficacy and safety of KI combined with chemotherapy for women breast cancer. CONCLUSION: This protocol for systematic review and meta-analysis will evaluate the efficacy and safety of KI combined with chemotherapy for women breast cancer, aiming to provide optimal therapy for women breast cancer patients.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Carcinoma/diagnóstico , Quimioterapia Adjuvante/métodos , Gerenciamento de Dados , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Neoplasias Esofágicas/patologia , Feminino , Humanos , Avaliação de Estado de Karnofsky , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
15.
Lancet Oncol ; 22(7): 959-969, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34118197

RESUMO

BACKGROUND: Oncogenic alterations in RET have been identified in multiple tumour types, including 1-2% of non-small-cell lung cancers (NSCLCs). We aimed to assess the safety, tolerability, and antitumour activity of pralsetinib, a highly potent, oral, selective RET inhibitor, in patients with RET fusion-positive NSCLC. METHODS: ARROW is a multi-cohort, open-label, phase 1/2 study done at 71 sites (community and academic cancer centres) in 13 countries (Belgium, China, France, Germany, Hong Kong, Italy, Netherlands, Singapore, South Korea, Spain, Taiwan, the UK, and the USA). Patients aged 18 years or older with locally advanced or metastatic solid tumours, including RET fusion-positive NSCLC, and an Eastern Cooperative Oncology Group performance status of 0-2 (later limited to 0-1 in a protocol amendment) were enrolled. In phase 2, patients received 400 mg once-daily oral pralsetinib, and could continue treatment until disease progression, intolerance, withdrawal of consent, or investigator decision. Phase 2 primary endpoints were overall response rate (according to Response Evaluation Criteria in Solid Tumours version 1·1 and assessed by blinded independent central review) and safety. Tumour response was assessed in patients with RET fusion-positive NSCLC and centrally adjudicated baseline measurable disease who had received platinum-based chemotherapy or were treatment-naive because they were ineligible for standard therapy. This ongoing study is registered with ClinicalTrials.gov, NCT03037385, and enrolment of patients with treatment-naive RET fusion-positive NSCLC was ongoing at the time of this interim analysis. FINDINGS: Of 233 patients with RET fusion-positive NSCLC enrolled between March 17, 2017, and May 22, 2020 (data cutoff), 92 with previous platinum-based chemotherapy and 29 who were treatment-naive received pralsetinib before July 11, 2019 (efficacy enrolment cutoff); 87 previously treated patients and 27 treatment-naive patients had centrally adjudicated baseline measurable disease. Overall responses were recorded in 53 (61%; 95% CI 50-71) of 87 patients with previous platinum-based chemotherapy, including five (6%) patients with a complete response; and 19 (70%; 50-86) of 27 treatment-naive patients, including three (11%) with a complete response. In 233 patients with RET fusion-positive NSCLC, common grade 3 or worse treatment-related adverse events were neutropenia (43 patients [18%]), hypertension (26 [11%]), and anaemia (24 [10%]); there were no treatment-related deaths in this population. INTERPRETATION: Pralsetinib is a new, well-tolerated, promising, once-daily oral treatment option for patients with RET fusion-positive NSCLC. FUNDING: Blueprint Medicines.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fusão Gênica , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-ret/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-ret/genética , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Pirimidinas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
16.
N Engl J Med ; 384(25): 2394-2405, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34081848

RESUMO

BACKGROUND: Poly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer. METHODS: We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival. RESULTS: A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease-free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P = 0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest. CONCLUSIONS: Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life. (Funded by the National Cancer Institute and AstraZeneca; OlympiA ClinicalTrials.gov number, NCT02032823.).


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Mutação em Linhagem Germinativa , Ftalazinas/uso terapêutico , Piperazinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Adulto , Antineoplásicos/efeitos adversos , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Mastectomia , Pessoa de Meia-Idade , Ftalazinas/efeitos adversos , Piperazinas/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Receptor ErbB-2
17.
BioDrugs ; 35(4): 459-468, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34152584

RESUMO

BACKGROUND: Infusion-related reactions (IRRs) are the most common adverse event (AE) associated with infusion of rituximab, an anti-CD20 monoclonal antibody. OBJECTIVE: Our objective was to evaluate the impact of dosing/infusion patterns and certain baseline characteristics on IRR occurrence during the first rituximab infusion administered as the biosimilar PF-05280586 (RTX-PF) or reference rituximab sourced from the EU (RTX-EU, MabThera®) in patients with CD20+ low-tumor-burden follicular lymphoma. PATIENTS AND METHODS: Rituximab (RTX-PF, n=196; RTX-EU, n=198) was administered (375 mg/m2) on days 1, 8, 15, and 22 (one cycle), with a follow-up period through 52 weeks. The relationships between infusion rate, drug exposure, and IRR incidence were assessed by logistic regression analysis and pharmacokinetic modeling and simulation. Baseline CD20 level, antidrug antibody (ADA) status, and tumor burden according to IRR occurrence (yes/no) were compared descriptively. RESULTS: Median rituximab infusion duration on day 1 was 3.50 h for each of the two groups. There was a positive correlation between infusion rate and all-grade IRRs occurring within 24 h after infusion (p < 0.0001). Patients who developed IRRs had a higher median baseline CD20+ level. IRR incidence was unaffected by baseline ADA status. Drug exposure did not predict IRR incidence. Baseline tumor burden was similar between patients with and without IRRs. CONCLUSIONS: Results of this analysis provide a better understanding of IRRs after the first rituximab (RTX-PF or RTX-EU) infusion and demonstrate a potential correlation of infusion rate and other factors with IRR at the individual and population levels. Infusion-rate escalation steps continue to be needed to manage IRRs. TRIAL REGISTRATION (DATE OF REGISTRATION): ClinicalTrials.gov Identifier: NCT02213263 (11 August 2014); and EudraCT: 2014-000132-41 (10 October 2014).


Assuntos
Antineoplásicos , Medicamentos Biossimilares , Anticorpos Monoclonais , Antígenos CD20 , Antineoplásicos/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Humanos , Rituximab/efeitos adversos
18.
Life Sci ; 280: 119760, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34166713

RESUMO

Cardiotoxicity is a major side effect of the chemotherapeutic drug doxorubicin (Dox), which is further exacerbated when it is combined with trastuzumab, a standard care approach for Human Epidermal growth factor Receptor-type 2 (HER2) positive cancer patients. However, the molecular mechanisms of the underlying cardiotoxicity of this combination are still mostly elusive. Increased oxidative stress, impaired energetic substrate uses and topoisomerase IIB inhibition are among the biological processes proposed to explain Dox-induced cardiomyocyte dysfunction. Since cardiomyocytes express HER2, trastuzumab can also damage these cells by interfering with neuroregulin-1 signaling and mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt and focal adhesion kinase (FAK)-dependent pathways. Nevertheless, Dox and trastuzumab target other cardiac cell types, such as endothelial cells, fibroblasts, cardiac progenitor cells and leukocytes, which can contribute to the clinical cardiotoxicity observed. This review aims to summarize the current knowledge on the cardiac signaling pathways modulated by these two antineoplastic drugs highly used in the management of breast cancer, not only focusing on cardiomyocytes but also to broaden the knowledge of the potential impact on other cells found in the heart.


Assuntos
Antineoplásicos/efeitos adversos , Cardiotoxicidade/etiologia , Doxorrubicina/efeitos adversos , Trastuzumab/efeitos adversos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cardiotoxicidade/metabolismo , Cardiotoxicidade/patologia , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Neuregulina-1/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Receptor ErbB-2/metabolismo , Transdução de Sinais/efeitos dos fármacos
19.
N Engl J Med ; 384(25): 2371-2381, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34096690

RESUMO

BACKGROUND: Sotorasib showed anticancer activity in patients with KRAS p.G12C-mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed in a subgroup of patients with non-small-cell lung cancer (NSCLC). METHODS: In a single-group, phase 2 trial, we investigated the activity of sotorasib, administered orally at a dose of 960 mg once daily, in patients with KRAS p.G12C-mutated advanced NSCLC previously treated with standard therapies. The primary end point was objective response (complete or partial response) according to independent central review. Key secondary end points included duration of response, disease control (defined as complete response, partial response, or stable disease), progression-free survival, overall survival, and safety. Exploratory biomarkers were evaluated for their association with response to sotorasib therapy. RESULTS: Among the 126 enrolled patients, the majority (81.0%) had previously received both platinum-based chemotherapy and inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1). According to central review, 124 patients had measurable disease at baseline and were evaluated for response. An objective response was observed in 46 patients (37.1%; 95% confidence interval [CI], 28.6 to 46.2), including in 4 (3.2%) who had a complete response and in 42 (33.9%) who had a partial response. The median duration of response was 11.1 months (95% CI, 6.9 to could not be evaluated). Disease control occurred in 100 patients (80.6%; 95% CI, 72.6 to 87.2). The median progression-free survival was 6.8 months (95% CI, 5.1 to 8.2), and the median overall survival was 12.5 months (95% CI, 10.0 to could not be evaluated). Treatment-related adverse events occurred in 88 of 126 patients (69.8%), including grade 3 events in 25 patients (19.8%) and a grade 4 event in 1 (0.8%). Responses were observed in subgroups defined according to PD-L1 expression, tumor mutational burden, and co-occurring mutations in STK11, KEAP1, or TP53. CONCLUSIONS: In this phase 2 trial, sotorasib therapy led to a durable clinical benefit without new safety signals in patients with previously treated KRAS p.G12C-mutated NSCLC. (Funded by Amgen and the National Institutes of Health; CodeBreaK100 ClinicalTrials.gov number, NCT03600883.).


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Piperazinas/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Piridinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Biomarcadores/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Piperazinas/efeitos adversos , Intervalo Livre de Progressão , Piridinas/efeitos adversos , Pirimidinas/efeitos adversos
20.
Medicine (Baltimore) ; 100(19): e25848, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106627

RESUMO

BACKGROUND: Cancer is the main cause of death worldwide, and chemotherapy is the basic method of treating cancer. However, chemotherapy-induced nausea and vomiting (CINV) is the most common side effect of chemotherapy, and conventional antiemetics for the treatment of CINV also have side effects. At present, a large number of randomized controlled trials have shown that Xiang-Sha-Liu-Jun-Zi (XSLJZ) can effectively treat CINV, but there is no systematic review. Therefore, this systematic review aims to discuss the effectiveness of XSLJZ in the treatment of CINV. METHODS: Search for relevant documents in the Chinese and English databases, and the search time is limited to March 2021. Databases include Embase, Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure, Chongqing VIP Information Resource Integration Service Platform, Wanfang Data, Chinese Biomedical Literature, etc. We will search the international clinical trial registration platform and the Chinese clinical trial registration platform to find ongoing and unpublished clinical trials. Randomized controlled trial of the efficacy of XSLJZ in the treatment of CINV were collected. After screening the literature according to the inclusion and exclusion criteria, two researchers independently extracted the data. The effective rate of treatment is the main outcome indicator of this study. The secondary indicators of this study include the incidence of adverse reactions and the improvement rate of quality of life. RevMan 5.3.5 software was used for statistical analysis. Grades of Recommendation, Assessment, Development, and Evaluation system will be used to evaluate the quality evidence for each outcome. RESULTS: This study will provide the latest evidence for the treatment of CINV by XSLJZ. CONCLUSION: : To evaluate the efficacy of XSLJZ in the treatment of CINV. UNIQUE INPLASY NUMBER: INPLASY202140079.


Assuntos
Antineoplásicos/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Antineoplásicos/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Neoplasias/tratamento farmacológico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...