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1.
Medicine (Baltimore) ; 100(35): e27121, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477154

RESUMO

BACKGROUND: This meta-analysis was performed to compare efficacy and tolerability between antiprogrammed cell death (PD-1)/programmed cell death-ligand-1 (PD-L1) + anticytotoxic T-lymphocyte-associated protein-4 (CTLA-4) treatment and chemotherapy in advanced lung cancer. METHODS: Cochrane Library, Embase, and PubMed databases were searched for potential articles. The fixed-effect model or random-effect model was adopted for pooled analysis based on the I2 and P-value. RESULTS: Six articles with 1338 patients were identified and subjected to meta-analysis. Compared with chemotherapy, anti-PD-1/PD-L1 + anti-CTLA-4 treatment could significantly improve the overall survival (hazard ratio [HR] = 0.78, 95%confidence interval [CI]: 0.71-0.84, P = .21) and progression-free survival (HR = 0.77, 95%CI: 0.71-0.83, P = .30) of advanced lung cancer patients. Moreover, there was no obvious difference in the incidence of 3 to 4 adverse events (AEs) serious adverse reactions (HR = 1.35, 95%CI: 0.66-2.74, P < .00001) between the 2 treatment groups, but the incidence rates of AEs leading to discontinuation (HR = 2.56, 95%CI: 1.53-4.30, P < .00001) and AEs leading to death (HR = 2.10, 95%CI: 1.21-3.63, P = .20) were higher. Furthermore, no remarkable differences in objective response rate (HR = 1.31, 95%CI: 0.97-1.77, P = .02) were observed between the 2 groups. CONCLUSION: Our meta-analysis revealed that PD-1/PD-L1 inhibitors plus CTLA-4 inhibitor could markedly improve the endpoint outcomes of patients compared with chemotherapy alone, and did not significantly increase the serious adverse reactions. Thus, it can serve as a new treatment strategy for advanced lung cancer.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Neoplasias Pulmonares/mortalidade
2.
Medicine (Baltimore) ; 100(35): e27134, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477162

RESUMO

RATIONALE: Chronic myelogenous leukemia (CML) with thrombocytosis and complex chromosomal translocation is extremely rare in clinical setting. Here, we reported the clinical and pathological characteristics of CML patients, which were characterized by thrombocytosis and complex Philadelphia chromosome translocation. Moreover, we also introduced our therapeutic schedule for this patient as well as review relative literature. PATIENT CONCERNS: A 24-year-old female presented with night sweating, fatigue, and intermittent fever for 1 month. DIAGNOSIS: Fluorescence in situ hybridization results revealed that breakpoint cluster region (BCR)-Abelson (ABL) gene fusion in 62% of the cells and karyotyping showed a complex 3-way 46, XY, t(9;22;11) (q34;q11;q13) [19/20] translocation. This patient was diagnosed with CML complicated with thrombocytosis and complex Philadelphia chromosome translocation. INTERVENTIONS: The patients received continuously oral imatinib mesylate tablets (400 mg) once a day. OUTCOMES: After treatment with imatinib for 3 months, the BCR/ABLIS was less than 0.1% and achieved major molecular response. Moreover, the BCR/ABLIS of this patient achieved major molecular response. The BCR/ABLIS values at 6 months and 12 months were less than 0.01% and 0.0032%, respectively. And no BCR/ABL fusion was detected in the next 2 years follow-up period. LESSONS: Imatinib might represent a preferred therapeutic option for CML patients with rare thrombocytosis and complex chromosomal translocation. In addition, BCR/ABL fusion gene examination in patients with thrombocytosis might represent an effective strategy to avoid the misdiagnosis of this specific CML population.


Assuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Cromossomo Filadélfia , Trombocitose/etiologia , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Adulto Jovem
3.
Medicine (Baltimore) ; 100(35): e27182, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477177

RESUMO

ABSTRACT: In this single-center retrospective study, we intended to evaluate the frequencies and characteristics of computed tomography findings of pancreatobiliary inflammation (PBI) in patients treated with lenvatinib and the relationship of these findings with treatment-planning changes.We included 78 patients (mean ±â€Šstandard deviation, 69.8 ±â€Š9.4 years, range: 39-84 years, 62 men) with hepatocellular carcinoma (n = 62) or thyroid carcinoma (n = 16) who received lenvatinib (June 2016-September 2020). Two radiologists interpreted the posttreatment computed tomography images and assessed the radiological findings of PBI (symptomatic pancreatitis, cholecystitis, or cholangitis). The PBI effect on treatment was statistically evaluated.PBI (pancreatitis, n = 1; cholecystitis, n = 7; and cholangitis, n = 2) was diagnosed in 11.5% (9/78) of the patients at a median of 35 days after treatment initiation; 6 of 9 patients discontinued treatment because of PBI. Three cases of cholecystitis and 1 of cholangitis were accompanied by gallstones, while the other 5 were acalculous. The treatment duration was significantly shorter in patients with PBI than in those without (median: 44 days vs. 201 days, P = .02). Overall, 9 of 69 patients without PBI showed asymptomatic gallbladder subserosal edema.Lenvatinib-induced PBI developed in 11.5% of patients, leading to a significantly shorter treatment duration. Approximately 55.6% of the PBI cases were acalculous. The recognition of this phenomenon would aid physicians during treatment planning in the future.


Assuntos
Antineoplásicos/efeitos adversos , Doenças Biliares/induzido quimicamente , Pancreatite/induzido quimicamente , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Biliares/diagnóstico por imagem , Doenças Biliares/epidemiologia , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico por imagem , Pancreatite/epidemiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
4.
BMJ Case Rep ; 14(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479888

RESUMO

Nilotinib is used as standard treatment in managing chronic myeloid leukaemia (CML). A 23-year-old man with CML and on nilotinib was admitted to the intensive care unit due to respiratory failure. Three years prior, he developed pleural effusion from dasatinib therapy thus, his CML regimen was changed to nilotinib. Although the pleural effusion had once improved, the chest imaging revealed left-dominant bilateral pleural effusion. Endotracheal intubation and left thoracic drainage were performed. Nilotinib treatment was discontinued, and approximately 60 hours later, nilotinib concentrations of 927 and 2092 ng/mL were determined in his blood and pleural effusion, respectively. Severe pleural effusion may be induced in patients administering nilotinib, and nilotinib concentrations in blood and pleural effusion can be elevated in patients with nilotinib-related pleural effusion. Cross-occurrence of pleural effusions needs to be monitored precisely, especially in patients who are switched to other tyrosine kinase inhibitors after dasatinib treatment.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Derrame Pleural , Adulto , Antineoplásicos/efeitos adversos , Dasatinibe/efeitos adversos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Derrame Pleural/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas , Adulto Jovem
5.
Mater Sci Eng C Mater Biol Appl ; 128: 112305, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474856

RESUMO

In spite of established evidence of the synergistic combination of hydrophobic anticancer molecule and microRNA for breast cancer treatment, their in vivo delivery has not been realized owing to their instability in the biological milieu and varied physicochemical properties. The present work reports folate targeted hybrid lipo-polymeric nanoplexes for co-delivering DTX and miR-34a. These nanoplexes exhibited a mean size of 129.3 nm with complexation efficiency at an 8:1 N/P ratio. The obtained nanoplexes demonstrated higher entrapment efficiency of DTX (94.8%) with a sustained release profile up to 85% till 48 h. Further, an improved transfection efficiency in MDA-MB-231 and 4T1 breast cancer cells was observed with uptake primarily through lipid-raft and clathrin-mediated endocytosis. Further, nanoplexes showed improved cytotoxicity (~3.5-5 folds), apoptosis (~1.6-2.0 folds), and change in expression of apoptotic genes (~4-7 folds) compared to the free treatment group in breast cancer cells. In vivo systemic administration of FA-functionalized DTX and FAM-siRNA-loaded nanoplexes showed an improved area under the curve (AUC) as well as circulation half-life compared to free DTX and naked FAM-labelled siRNA. Acute toxicity studies of the cationic polymer showed no toxicity at a dose equivalent to 10 mg/kg based on the hematological, biochemical, and histopathological examination.


Assuntos
Antineoplásicos , Neoplasias da Mama , MicroRNAs/administração & dosagem , Nanopartículas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Docetaxel/farmacologia , Portadores de Fármacos/uso terapêutico , Feminino , Ácido Fólico , Humanos , MicroRNAs/genética , Polímeros/uso terapêutico
6.
Anticancer Res ; 41(9): 4431-4438, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475065

RESUMO

BACKGROUND/AIM: Although still controversial, the current treatment for locally advanced neuroendocrine carcinoma of the cervix (NECC) relies on chemoradiation (CRT). The aim of this study is to evaluate the alternative role of combined chemotherapy and surgery in treating NECC. PATIENTS AND METHODS: This is a retrospective series of patients undergoing radical surgery after neoadjuvant chemotherapy (NACT) for locally advanced NECC (stages IIB-IVA). Histological examination and immunohistochemistry were performed on surgical specimens to confirm diagnosis. Systematic literature search was conducted to identify other cases treated with chemotherapy and surgery. RESULTS: Seven patients with a mean age of 49 years were identified. The mean greatest diameter at diagnosis was 59.3±24.7 mm. FIGO stage was IIB in 14.3% of patients, IIIB in 28.6%, IIIC in 42.9%, and IVA in 14.3%. The response to NACT was partial, ranging from 50% to 80%. Neuroendocrine markers were expressed in all cases. The mean progression-free survival (PFS) and overall survival (OS) were 15.0±30.6 months and 26.3±36.4 months, respectively. Eleven studies encompassing a total of 27 patients met eligibility criteria for the systematic review. CONCLUSION: Surgery after NACT for locally advanced NECC may yield similar outcomes compared to CRT. The benefit of performing surgery as a primary approach could lie in the possibility of reserving CRT for recurrences. Since randomized clinical trials are difficult to be designed, an expert consensus is required to address the non-inferiority of radical surgery over CRT.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/cirurgia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Carcinoma Neuroendócrino/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
7.
Anticancer Res ; 41(9): 4535-4542, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475080

RESUMO

BACKGROUND/AIM: Due to the SARS-CoV-2 pandemic, many scientific committees proposed neoadjuvant therapy (NACT) bridging treatment as a novel strategy and indication. The aim of the study was to evaluate the impact of COVID-19 pandemic on breast cancer patients undergoing NACT. PATIENTS AND METHODS: All breast cancer patients referred to two Breast Units during COVID-19-pandemic were enrolled. RESULTS: Out of 814 patients, 43(5.3%) were enrolled in the COVID-19-group and compared with 94 (7.9%) similar Pre-COVID-19 patients. We observed a reduction in the number of patients undergoing NACT, p=0.0019. No difference was reported in terms of clinical presentation, indications, and tumor response. In contrast, a higher number of vascular adverse events was reported (6.9% vs. 0% p=0.029). Immediate breast cancer reconstructions following invasive surgery suffered a significant slowdown (5.9% vs. 47.7%, p=0.019). CONCLUSION: COVID-19 caused a reduction in the number of patients undergoing NACT, with no changes in terms of indications, clinical presentation, and tumor response. Furthermore, there was an increased incidence of vascular events.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , COVID-19/epidemiologia , Mamoplastia/estatística & dados numéricos , Terapia Neoadjuvante/estatística & dados numéricos , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , COVID-19/complicações , Tratamento Farmacológico/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Pandemias , Estudos Retrospectivos , Resultado do Tratamento
8.
Anticancer Res ; 41(9): 4543-4548, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475081

RESUMO

BACKGROUND/AIM: Adverse event (AE) frequencies observed in interventional clinical trials are difficult to interpret when the placebo control is missing. MATERIALS AND METHODS: Systematic literature review of AEs reported from the placebo arms of randomized cancer trials between 2008 and 2021. Imputation of missing values assuming normal distribution of hemoglobin values. RESULTS: Anemia grade 1 or higher was reported in 46 of 100 placebo monotherapy cohorts with a mean frequency of 23.4% (SD=27%) of the enrolled patients. The reported frequency depended on the type of cancer; other demographic variables had no significant influence on anemia frequency. CONCLUSION: External controls for anemia in clinical trials should be disease specific.


Assuntos
Anemia/epidemiologia , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Adolescente , Adulto , Idoso , Anemia/induzido quimicamente , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
9.
Anticancer Res ; 41(9): 4555-4562, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475083

RESUMO

BACKGROUND/AIM: While there is increasing evidence supporting the role of several first- and second-line treatment regimens for advanced hepatocellular carcinomas (HCC), the clinical relevance of rechallenge treatment with previously administered drugs, however, remains to be explored. PATIENTS AND METHODS: Five consecutive patients with advanced HCC who received lenvatinib rechallenge treatment after ramucirumab were assessed. RESULTS: All patients were clinically diagnosed with failure after ramucirumab treatment, and the frequencies of ramucirumab administration before lenvatinib re-administration ranged from 3 to 11. The alfa-fetoprotein level in four of five patients decreased 1 month after the lenvatinib rechallenge. Radiological findings via the modified Response Evaluation Criteria in Solid Tumors showed stable diseases in four patients and a partial response in one. CONCLUSION: Rechallenge treatment with lenvatinib after ramucirumab can be effective, and may be a treatment option for HCC in cases wherein the disease progressed after an initial response to lenvatinib treatment.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/administração & dosagem , Quinolinas/administração & dosagem , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Estudos Retrospectivos , Falha de Tratamento , Resultado do Tratamento , alfa-Fetoproteínas/metabolismo
10.
Rinsho Ketsueki ; 62(8): 1012-1023, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497187

RESUMO

The chronic myeloid leukemia (CML) therapeutic landscape has dramatically changed with the development of tyrosine kinase inhibitors (TKIs), which allows for a near-normal life expectancy. Five TKIs have been currently approved for CML treatment in Japan, of which four have been indicated as first-line therapy (i.e., imatinib, nilotinib, dasatinib, and bosutinib). Nowadays, the long-term prognosis of patients with CML is determined not by the primary disease but rather by the comorbidities and treatment-related adverse events (AEs), including cardiovascular events. Assessment of risk profile and comorbidities at diagnosis is essential for the appropriate choice of TKI and long-term survival management. The ability of some patients who achieve deep molecular responses to discontinue therapy successfully is well documented. Long-term treatment-free remission with continued response to TKI therapy is now recognized as the most optimal treatment benefit for some patients.This article discusses treatment strategies, AE management, and future perspectives based on the latest CML treatment guidelines.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos/uso terapêutico , Dasatinibe/uso terapêutico , Humanos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico
11.
Rinsho Ketsueki ; 62(8): 1024-1028, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497188

RESUMO

BCR-ABL tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML). Currently, five BCR-ABL TKIs are approved for use in patients with CML, but the long-term use of these TKIs is associated with various cardiovascular events. Typical cardiovascular adverse events include pulmonary hypertension caused by dasatinib and arterial occlusive diseases caused by nilotinib and ponatinib. Although mechanisms of cardiovascular adverse events of BCR-ABL TKIs in the treatment of CML have not been clarified, differences in their inhibitory activities on off-target kinases, including those involved in vascular function, may be related to individual safety profiles. Arterial occlusive diseases are common in patients with a history of cardiovascular disease and risk of atherosclerosis. Arterial occlusive diseases, such as ischemic heart disease, ischemic cerebral disease, and peripheral arterial occlusive disease, worsen the prognosis and quality of life of patients with CML. Therefore, appropriate management strategies are required. This paper outlines cardiovascular adverse events associated with TKI treatment, including arterial obstructive diseases, pulmonary arterial hypertension, and QT interval prolongation.


Assuntos
Antineoplásicos , Hipertensão Pulmonar , Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos/uso terapêutico , Dasatinibe/uso terapêutico , Proteínas de Fusão bcr-abl , Humanos , Hipertensão Pulmonar/induzido quimicamente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Qualidade de Vida
12.
Rinsho Ketsueki ; 62(8): 1070-1076, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497193

RESUMO

The prognosis of patients with follicular lymphoma (FL) has improved over the last decades. However, most patients with FL will eventually relapse. The management of FL is mainly determined by clinical stage and tumor burden. For localized-stage patients, an involved-field radiation therapy is recommended. For advanced-stage low tumor burden patients, watchful waiting remains the standard treatment, whereas rituximab monotherapy may be an alternative option. Immuno-chemotherapy combined with rituximab maintenance has been the standard care for patients with high tumor burden. Recently, the novel anti-CD20 monoclonal antibody obinutuzumab was approved for the treatment of FL. Obinutuzumab with chemotherapy followed by obinutuzumab maintenance is considered one of the standard therapeutic options. After relapse or progression, it is necessary to consider a treatment strategy based on several disease-related, treatment-related, and patient-related factors. During the last decade, the development of biological knowledge and use of molecularly targeted agents offer new therapeutic perspectives with chemo-free strategies. This review highlights the current standards for the treatment of FL.


Assuntos
Antineoplásicos , Linfoma Folicular , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Linfoma Folicular/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Rituximab/uso terapêutico
13.
Rinsho Ketsueki ; 62(8): 1085-1093, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497195

RESUMO

Chronic lymphocytic leukemia (CLL) is a rare type of lymphoid malignancy among Japanese. Its clinical course is indolent, and the prognosis is good. The two types of CLL based on the mutation status of the IgH gene V segment have been documented in the literature. Then, the del (17p)/TP53 subtype is emphasized, and the treatment strategy for the three subtypes differs. Recent knowledge on molecular pathogenesis facilitated the usage of Bruton's tyrosine kinase (BTK) and BCL2 inhibitors for the treatment of CLL. A better response can be obtained with the use of these novel agents, resulting in a higher rate of negativity for measurable residual disease (MRD). The treatment strategy based on MRD negativity and the treatment outcomes of CLL will improve in future.


Assuntos
Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Tirosina Quinase da Agamaglobulinemia , Antineoplásicos/uso terapêutico , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico
14.
Nihon Yakurigaku Zasshi ; 156(5): 303-311, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34470936

RESUMO

Cabozantinib (CAB) is a receptor tyrosine kinase inhibitor with activity against MET, VEGFR2, and AXL, among others. This drug is considered to exert excellent antitumor effects by inhibiting these targets simultaneously. Significant improvement in the primary endpoint (overall survival or PFS) were observed in patients on CAB in comparison with controls in a phase-III study in patients with renal cell carcinoma, progressed after treatment with anti-angiogenic agents, and in another phase-III study in patients with previously treated, advanced hepatocellular carcinoma. These results led to the approval of CAB in Japan in 2020 as a therapeutic agent for unresectable or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma progressed after cancer chemotherapy, under the trade name of CABOMETYX® (20 mg, and 60 mg tablets). It has been suggested that CAB may modulate the immune system in favor of antitumor immunity and combined use with PD-1 checkpoint inhibitors may exert a synergistic effect. In a phase-III study that examined the efficacy of combination therapy with CAB and nivolumab in treatment-naive patients with advanced renal cell carcinoma, progression-free survival was significantly increased in patients on combination therapy over patients on sunitinib monotherapy. Three global phase-III clinical studies of combination therapy with atezolizumab and CAB in patients with non-small cell lung cancer, castration-resistant prostate cancer, and renal cell carcinoma, are in progress to confirm the efficacy of CAB.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Hepáticas , Neoplasias Pulmonares , Anilidas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Piridinas
15.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 620-627, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34494535

RESUMO

Multi-drug resistance(MDR)refers to the loss of sensitivity of tumor cells to traditional chemotherapeutics agents under the mediation of various mechanisms,resulting in the reduction of chemotherapy efficacy.Current studies suggest that a variety of factors,including cell membrane transporter-mediated efflux of anti-tumor drugs,special microenvironment in tumor tissue,DNA self-repair and anti-apoptotic process,and epithelial-mesenchymal cell transformation,may contribute to the formation of MDR.Cell membrane transporter-mediated drug efflux refers to an increase in the amount of anti-tumor drug pumped out of the cell through the up-regulation of the ATP-binding cassette transporter on tumor cell membrane,which reduces the concentration of the drug in the cell,thus forming MDR.An effective method to inhibit the efflux pump caused by overexpression of membrane transporters plays an important role in overcoming MDR.As a promising drug delivery system,multifunctional nanoparticles have demonstrated many advantages in antitumor therapy.Meanwhile,nanoparticles with tailored design are capable of overcoming MDR when combined with a variety of strategies.This paper described in detail the studies relevant to the use of multifunctional nano-sized drug delivery system combined with different strategies,such as co-delivery of agents,external responsiveness or target modification for intervention with efflux pump in order to reverse MDR.This paper provides reference for the development of nano-sized drug delivery system and the formulation of reversal strategy in the future.


Assuntos
Antineoplásicos , Nanopartículas Multifuncionais , Nanopartículas , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Membrana Celular , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Proteínas de Membrana Transportadoras/farmacologia , Proteínas de Membrana Transportadoras/uso terapêutico , Neoplasias/tratamento farmacológico , Microambiente Tumoral
16.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(9): 762-768, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34530556

RESUMO

Tumor rupture is a common clinical event in the process of tumorigenesis, progression, diagnosis and treatment of gastrointestinal stromal tumor, which is closely associated with tumor recurrence, metastasis and poor prognosis. Tumor rupture may be associated with some intrinsic biological aggressiveness qualities, such as large tumor size, high mitotic count, and KIT exon 11 deletion mutations involving codons 557 and 558, and may be relatively more frequent with small intestine GIST and excellent response to imatinib neoadjuvant therapy resulting in tumor tissue rapid liquefacient and necrosis. The triggering factors involve sudden increase in abdominal pressure, external pressure, collision and improper surgical operation, etc. Tumor rupture is considered as an important risk factor of recurrence after macroscopically complete resection of tumor, and an indication for determining interval or even lifelong adjuvant therapy with imatinib according to guidelines. However, there is no consensus or universally accepted definition of tumor rupture, and, consequently, its incidence varies greatly across reported series and lacks detailed epidemiological data. Without pre-defined criteria, it is difficult to assess the clinical significance of rupture. We reviewed the relevant literature and international guidelines, and generally divided tumor rupture into spontaneous rupture and iatrogenic rupture. Based on the Oslo criteria, we proposed the following six definitions for tumor rupture: (1) tumor fracture or spillage; (2) blood-stained ascites; (3) gastrointestinal perforation at the tumor site; (4) microscopic infiltration of an adjacent organ; (5) intralesional dissection or piecemeal resection; (6) incisional biopsy. The following types of minor defects of tumor integrity should not be defined as rupture: (1) mucosal defects or spillage contained within the gastrointestinal lumen; (2) microscopic tumor penetration of the peritoneum or iatrogenic damage only to the serosa; (3) uncomplicated transperitoneal needle biopsy; (4) R1 resection. In addition, we further emphasize the importance of identifying risk factors of tumor rupture, prevention and positive intervention.


Assuntos
Antineoplásicos , Tumores do Estroma Gastrointestinal , Antineoplásicos/uso terapêutico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Mesilato de Imatinib/uso terapêutico , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Ruptura Espontânea
17.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(9): 775-782, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34530558

RESUMO

Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.


Assuntos
Antineoplásicos , Tumores do Estroma Gastrointestinal , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante , Estudos Transversais , Feminino , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Mesilato de Imatinib/uso terapêutico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico
18.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(9): 789-795, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34530560

RESUMO

Objective: To explore the significance of circulating tumor cell (CTC) monitoring in evaluating the efficacy of targeted therapy for gastrointestinal stromal tumor (GIST). Methods: A prospective cohort study was performed. The data of patients with locally advanced GIST or liver metastasis who were admitted to The Affiliated Hospital of Nantong University from August 2013 to December 2018 were collected. Inclusion criteria: (1) patients aged older than 18 years; (2) patients who were diagnosed with GIST based on pathology; (3) patients without surgery, whose preoperative imaging evaluation of GIST found the violations of the surrounding organs or partial transfer of an estimated difficulty to achieve R0 resection, or the maximum diameter of the tumor > 10 cm, or the liver metastasis, or the expectation of higher risk of surgical complications; (4) patients who were treated with the imatinib 400 mg/d for the first time; (5) Eastern Cooperative Oncology Group (ECOG) score of 0-2. Exclusion criteria: (1) genetic testing revealed a D842V mutation in exon 18 of the PDGFRA gene; (2) alanine aminotransferase and/or aspartate aminotransferase > 2.5 times the normal upper limit; (3) serum total bilirubin >1.5 times of normal upper limit; (4) neutrophil count < 1.5×10(9)/L, or platelet count < 75×10(9)/L, or hemoglobin < 60 g/L; (5) creatinine > normal upper limit; (6) patients had serious cardiovascular and cerebrovascular diseases within 12 months before enrollment; (7) female patients were pregnant or lactating; (8) patients suffered from other serious acute and chronic physical or mental problems, and were not suitable for participating in this study judged by researchers. The patients who could not tolerate treatment regimen, or developed serious adverse reactions and did not follow the medication scheme after enrollment were excluded. Before imatinib treatment and 1-month and 2-month after treatment, quantitative PCR was used to detect the DOG-1 expression of monocytes in peripheral blood, and the ratio of DOG-1/ß-actin > 3×10(-5) was used as the CTC positive threshold of GIST. The positive rate of CTC, the efficacy of imatinib treatment (complete response, partial response, stable disease, progressive disease, and occurrence of adverse reactions), and the relationship between CTC positive rate and clinicopathological characteristics of patients were analyzed. Furthermore, the ratio of DOG-1 decrease/baseline DOG-1 after 1-month of treatment was used as an indicator to evaluate whether targeted therapy was effective. The receiver operating characteristic (ROC) curve was rendered, and the area under the curve (AUC) was calculated. Results: A total of 68 GIST patients were enrolled in this study, including 39 cases of locally advanced GIST and 29 cases with liver metastases, 32 males and 36 females with the mean age of (51.2±11.8) (range 31 to 74) years. After 2-month of imatinib treatment, 43 cases were evaluated as partial response, 11 cases as stable disease, and 14 cases as progressive disease, with an effective rate of 79.4% (54/68). During the treatment of imatinib, the incidence of grade 3 or higher adverse reactions was 22.1% (15/68), including 12 cases of grade 3 neutropenia and 3 of grade 4 drug eruption, which were all relieved after conservative treatment. The positive rates of CTC in 68 patients before treatment, 1-month and 2-month after treatment were 66.2% (45/68), 41.2% (28/68) and 23.5% (16/68), respectively. The positive rate of CTC was associated with tumor size, liver metastasis, mitotic count and risk level (all P<0.05). By analyzing the effective group and the ineffective group of targeted therapy, it was found that the positive rate of CTC in the effective group showed a decreasing trend, while the positive rate of CTC in the ineffective group showed an increasing trend. The AUC of predicting the efficacy of targeted therapy for GIST was 0.823 by detecting the change trend of CTC 1-month after treatment (P<0.001). When the DOG-1 content decreased by more than 57.5% 1-month after treatment, it can be used as an indicator to judge the effectiveness of the treatment, whose sensitivity was 72.2% and specificity was 100%. Conclusion: The detection of peripheral blood CTC can evaluate the efficacy of targeted therapy in GIST patients and can provide decision-making basis for further clinical treatment.


Assuntos
Antineoplásicos , Tumores do Estroma Gastrointestinal , Células Neoplásicas Circulantes , Idoso , Antineoplásicos/uso terapêutico , Feminino , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Humanos , Mesilato de Imatinib/uso terapêutico , Lactação , Masculino , Estudos Prospectivos
19.
Zhonghua Wei Chang Wai Ke Za Zhi ; 24(9): 804-813, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34530562

RESUMO

Objective: To investigate the clinicopathological features of gastrointestinal stromal tumor (GIST) with KIT/PDGFRA "homozygous mutation", the efficacy of targeted therapy and the prognosis. Methods: A retrospective cohort study and propensity score matching were used. "Homozygous mutation" was defined as the detection of KIT/PDGFRA gene status of GIST by Sanger sequencing, which showed that there was only mutant gene sequence in the sequencing map, lack of wild-type sequence or the peak height of mutant gene sequence was much higher than that of wild-type gene sequence (> 3 times). "Heterozygous mutation" was defined as the mutant gene sequences coexisted with wild type gene sequences, and the peak height was similar (3 times or less). The clinicopathological data and follow-up information of 92 GIST patients with KIT/PDGFRA "homozygous mutation" were collected from 4 hospitals in Shanghai from January 2008 to May 2021 (Renji Hospital, Shanghai Jiaotong University School of Medicine: 70 cases; Zhongshan Hospital, Fudan University: 14 cases; Changhai Hospital, Naval Military Medical University: 6 cases and Ruijin Hospital, Shanghai Jiaotong University School of Medicine: 2 cases). Patients with perioperative death, other malignancies, and incomplete clinicopathological information were excluded. The clinicopathological features of the patients and the efficacy of targeted drug therapy were observed and analyzed. The efficacy was evaluated using Choi criteria, which were divided into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). In addition, a total of 230 patients with high-risk GIST with "heterozygous mutation" in exon 11 of KIT gene and 117 patients with recurrent or metastatic GIST with "heterozygous mutation" in exon 11 of KIT gene were included. The propensity score matching method was used to match GIST patients with "heterozygous" and "homozygous" mutations in exon 11 of KIT gene (1∶1) for survival analysis. The disease-free survival (DFS) between two groups of high-risk GIST patients who underwent complete surgical resection were compared. And progression-free survival (PFS) in patients with recurrent or metastatic GIST were compared. Results: Of the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 58 were males and 34 were females, with a median onset age of 62 (31-91) years. Primary GIST 83 cases. Primary high-risk GIST (53 cases), metastatic GIST (21 cases) and recurrent GIST (9 cases) accounted for 90.2% (83/92). There were 90 cases of KIT gene"homozygous mutation" (exon 11 for 88 cases, exon 13 for 1 case, exon 17 for 1 case), and 2 cases of PDGFRA gene "homozygous mutation" (exon 12 for 1 case, exon 18 for 1 case). The median follow-up time was 49 (8-181) months. Among the 61 cases of primary localized GIST undergoing complete surgical resection, 2 cases were intermediate-risk GIST, 5 cases were low-risk GIST, and 1 case was very low-risk GIST, of whom 1 case of intermediate-risk GIST received 1-year adjuvant imatinib mesylate (IM) therapy after operation, and no tumor recurrence developed during the follow-up period. The remaining 53 cases were high-risk GIST, and follow-up data were obtained from 50 cases, of whom 22 developed tumor recurrence during follow-up. Of 9 patients directly receiving neoadjuvant targeted therapy (IM or avapritinib), 5 had complete imaging follow-up data, and the evaluation of efficacy achieved PR. Of all the 92 GIST cases with KIT/PDGFRA "homozygous mutation", 50 (54.4%) had tumor metastasis or tumor recurrence or progression during follow-up, and 12 (13.0%) died of the tumor. Survival analysis combined with propensity score showed that in 100 cases of high-risk GISTs with complete resection, GISTs with "homozygous mutation" in exon 11 of KIT gene had shorter disease-free survival (DFS) than GISTs with "heterozygous mutation" in exon 11 of KIT gene (median DFS: 72 months vs. 148 months, P=0.015). In 60 cases of recurrent or metastatic GISTs with KIT gene exon 11 mutation, IM was used as the first-line treatment, and the progression-free survival (PFS) of GISTs with "homozygous mutation" was shorter compared to GISTs with "heterozygous mutation" (median PFS: 38 months vs. 69 months, P=0.044). The differences were statistically significant. Conclusions: "Homozygous mutation" in KIT/PDGFRA gene is associated with the progression of GIST. The corresponding targeted therapeutic drugs are still effective for GIST with KIT/PDGFRA gene "homozygous mutation". Compared with GIST patients with "heterozygous mutation" in KIT exon 11, GIST patients with "homozygous mutation" in KIT exon 11 are more likely to relapse after surgery and to develop resistance to IM. Therefore, it is still necessary to seek more effective treatment methods for this subset of cases.


Assuntos
Antineoplásicos , Tumores do Estroma Gastrointestinal , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , China , Feminino , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Prognóstico , Proteínas Proto-Oncogênicas c-kit/genética , Pirazóis , Pirróis , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Estudos Retrospectivos , Triazinas
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