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1.
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
2.
Anticancer Res ; 41(9): 4287-4294, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475048

RESUMO

BACKGROUND/AIM: Sunitinib continues to be administered as a first-line therapeutic agent in metastatic renal cell carcinoma (mRCC). This study examined the potential role of p53 in sunitinib resistance and as a predictive marker in mRCC. MATERIALS AND METHODS: We analysed the effects of p53 knockout on sunitinib resistance. p53 expression in 53 mRCC patients receiving first-line sunitinib was determined immunohistochemically. We performed in silico analysis to examine the predictive value of p53 in mRCC. RESULTS: WST-1 assays showed that p53 knockout decreased sensitivity to sunitinib. Sunitinib and nutlin-3 together suppressed cell growth. Immunohistochemistry revealed 11 p53-positive cases among 53 patients with mRCC. Kaplan-Meier analysis showed that p53-positive cases tended to be associated with poor progression-free survival (PFS) after first-line sunitinib treatment. In the JAVELIN 101 study, TP53 mutation was significantly associated with poor PFS after sunitinib treatment. CONCLUSION: p53 may be involved in sunitinib resistance and represent a valuable marker for sunitinib treatment in mRCC.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Imidazóis/farmacologia , Neoplasias Renais/tratamento farmacológico , Piperazinas/farmacologia , Sunitinibe/farmacologia , Proteína Supressora de Tumor p53/genética , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Proliferação de Células/efeitos dos fármacos , Simulação por Computador , Sinergismo Farmacológico , Feminino , Técnicas de Inativação de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos
3.
Gan To Kagaku Ryoho ; 48(9): 1145-1151, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34521793

RESUMO

Although cytokine therapy has been a common drug therapy for renal cell carcinoma for long since the 1980s, the evidence for the rationale of this therapy has been limited. Currently, 7 molecular targeted drugs(ie, sorafenib, sunitinib, axitinib, pazopanib, cabozantinib, everolimus, and temsirolimus)are available in Japan. Among these molecular targeted drugs, we clinically evaluated 5 tyrosine kinase inhibitors(ie, sorafenib, sunitinib, axitinib, pazopanib, and cabozantinib)in terms of their effects on blood pressure and the response rate by Bayes-mixed treatment comparison meta-analysis(Bayes- MTC analysis)to develop the decision-making model for the optimal treatment selection. Cabozantinib and axitinib exerted the greatest effect on blood pressure, and their probability of affecting blood pressure was 1.7 to 2 times higher than the probability of sunitinib. Among the 5 tyrosine kinase inhibitors, the effects of sunitinib and sorafenib on blood pressure were small. According to the results of clinical trials in Japan, hypertension was observed in 27.5% of patients treated with sorafenib, 51.0% with sunitinib, and 75.7% with axitinib. Our analysis also showed similar results. This study demonstrated that Bayes-MTC analysis is a useful tool enabling not only direct evaluation but also indirect evaluation.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Antineoplásicos/uso terapêutico , Teorema de Bayes , Pressão Sanguínea , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases/uso terapêutico
4.
Hinyokika Kiyo ; 67(7): 309-312, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34353011

RESUMO

We report a case of Stauffer syndrome-like findings in a patient with metastatic renal carcinoma treated by surgery and molecular targeted therapy. The patient was a 58-year-old woman diagnosed with renal carcinoma with multiple metastases. She had hepatosplenomegaly and hepatic dysfunction with elevated serum liver enzyme and IL-6 levels. Treatment with temsirolimus and axitinib reduced the size of the local and metastatic tumors and simultaneously improved the hepatosplenomegaly. The local tumor was excised by laparoscopic nephrectomy, treated with axitinib and then with nivolumab. With the reduction in the metastatic tumor size, serum liver enzyme and IL-6 levels decreased. It was suggested that molecular targeted therapy is an effective treatment when the findings of metastatic renal cell carcinoma, are similar to those of Stauffer syndrome.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Axitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Nivolumabe/uso terapêutico
5.
Am J Case Rep ; 22: e932924, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34358221

RESUMO

BACKGROUND The efficacy and safety of re-challenge with immune checkpoint inhibitors after immune-related adverse events have not been established. We report a case of successful re-administration of nivolumab in metastatic renal cell carcinoma after discontinuation due to immune-related adverse events. CASE REPORT Laparoscopic nephrectomy was performed on a 52-year-old man diagnosed with renal cell carcinoma pT1bN0M0. After surgery, left adrenal and lung metastases appeared. Nivolumab was administered as a sixth-line therapy, and he achieved a partial response, but interstitial pneumonia occurred. He was diagnosed with grade 2 immune-related adverse events, and nivolumab treatment was discontinued. Interstitial pneumonia was well controlled by steroids. He maintained a partial response for a long time, and the lung metastases disappeared 7 months after discontinuation. However, bilateral lung metastases reappeared 10 months after the discontinuation. We decided to re-administer nivolumab, while carefully monitoring the patient and fully explaining the risk of recurrence of immune-related adverse events. After 5 cycles of re-administration, computed tomography revealed a reduction in metastases without re-activation of interstitial pneumonia. He experienced a grade 1 fever the day after re-administration, but continued nivolumab therapy without other adverse events. After 7 cycles of re-administration, the lung metastases increased, and nivolumab treatment was terminated. Two months later, a grade 2 interstitial pneumonia recurred, but improved rapidly with oral steroids. CONCLUSIONS For patients who have discontinued immune checkpoint inhibitors due to immune-related adverse events, re-challenge of immune checkpoint inhibitors may be an option after explaining the risk of relapse of immune-related adverse events.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Doenças Pulmonares Intersticiais , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Doenças Pulmonares Intersticiais/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Nivolumabe/efeitos adversos
7.
In Vivo ; 35(5): 2855-2862, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410978

RESUMO

BACKGROUND/AIM: The relationship between albumin-to-alkaline phosphatase ratio (AAPR) and the outcome of patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors remains unresolved. We aimed to clarify the prognostic role of AAPR in nivolumab monotherapy for previously treated mRCC. PATIENTS AND METHODS: We retrospectively evaluated 60 patients with mRCC treated with nivolumab after failure of at least one molecular targeted therapy. The patients were stratified into two groups based on the baseline AAPR. The threshold of AAPR was determined using receiver-operating characteristics and Youden index analyses. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) of nivolumab therapy were compared between the high and low AAPR groups. RESULTS: The threshold of AAPR was set at 0.3, and 20 patients (33%) were assigned to the low AAPR group. The median OS and PFS were significantly lower in the low AAPR group than those in the high group (OS: 8.3 months vs. not reached, p<0.0001; PFS: 2.9 vs. 10.4 months, p=0.0006). Moreover, ORR was significantly lower in the low AAPR group than in the high group (16% vs. 45%, p=0.0397). Multivariate analyses further showed that AAPR was an independent factor for OS [HR=0.27 (95% CI=0.09-0.77), p=0.0151] but not for PFS (p=0.174). CONCLUSION: Baseline AAPR was significantly associated with outcome in patients with mRCC receiving nivolumab monotherapy and may, therefore, constitute an effective prognostic factor for nivolumab treatment.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Albuminas , Fosfatase Alcalina , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Prognóstico , Estudos Retrospectivos
8.
In Vivo ; 35(5): 2969-2974, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410996

RESUMO

BACKGROUND: We report two cases in which severe skin disorders developed during sorafenib treatment in patients with renal cell carcinoma (RCC) who had previously received nivolumab. CASE REPORT: Case 1: A 50-year-old man with RCC received nivolumab as the fifth-line therapy followed by sorafenib as the sixth-line therapy. On day 15 of sorafenib administration, the patient was hospitalized with systemic erythema multiforme, acne-like skin rash, and hand-foot syndrome. Case 2: A 40-year-old man with RCC received nivolumab as the second-line therapy followed by sorafenib as the fifth-line treatment. On day 12 of sorafenib administration, the patient was hospitalized with an acne-like skin rash and hand-foot syndrome. The skin disorders in the two cases improved within 2-3 weeks after sorafenib discontinuation and the start of treatment with topical and oral steroids. CONCLUSION: When using sorafenib in patients previously treated with nivolumab, close attention should be paid to the onset of serious skin disorders.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Adulto , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Niacinamida/efeitos adversos , Nivolumabe/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Sorafenibe/efeitos adversos , Resultado do Tratamento
9.
In Vivo ; 35(5): 2981-2990, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410998

RESUMO

BACKGROUND/AIM: Immunotherapy with checkpoint inhibitors is currently considered a cornerstone of metastatic renal clear cell cancer (mRCC) therapy. Despite the general improvement in the survival of patients with mRCC, there are some clinical situations that have not been specifically evaluated in clinical trials, such as the use of everolimus before nivolumab. PATIENTS AND METHODS: We performed a retrospective analysis evaluating the efficacy of nivolumab in the real-world setting, including a subset of patients with previous mTOR inhibitor therapy. RESULTS: From a total of 56 patients, 25 were pre-treated with everolimus before receiving nivolumab. The overall progression-free survival (PFS), overall survival (OS), and objective response rate were 10.3, 21.3 months, and 34%, respectively. There were no statistically significant differences in patients who were or were not pre-treated with everolimus. CONCLUSION: mRCC patients should be treated with checkpoint inhibitors and prior use of mTOR inhibitors should not be a definitive exclusion criterium.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Nivolumabe , Estudos Retrospectivos , Serina-Treonina Quinases TOR , Resultado do Tratamento
10.
Aktuelle Urol ; 52(5): 439-444, 2021 09.
Artigo em Alemão | MEDLINE | ID: mdl-34428826

RESUMO

Renal cell carcinoma is a common malignant tumour, whose incidence is steadily increasing. Whilst operative techniques have recently improved, including possibilities of renal preservation and minimally invasive surgery, no use has been shown for adjuvant treatment strategies. When local therapies are not suitable in relapsed or metastatic disease, medical drug treatment is indicated. The first immunologic treatment for renal cell carcinoma consisted of cytokines and overall survival amounted to a median of 13 months. Over the last decade, tyrosine kinase inhibitors (TKI), which inhibit the tumour vasculature, dominated the therapeutic area and raised the clinical discussion about the best sequential pattern. More recently, checkpoint inhibitors (CPI) have set a new standard as therapeutic tools in renal cell cancer. Modern first-line therapies consist of checkpoint inhibitor-based combinations, which have shifted the median overall survival expectation to >40 months. However, tyrosine kinase inhibitors have retained their therapeutic value as combination partners and also as monotherapy in individual cases. One combined immunotherapy and 3 combinations of a checkpoint inhibitor and a TKI are currently approved in Germany.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/tratamento farmacológico , Alemanha , Humanos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Recidiva Local de Neoplasia
11.
Medicine (Baltimore) ; 100(31): e26788, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397830

RESUMO

BACKGROUND: In this study, we evaluated the efficacy and safety of histone deacetylase inhibitors (HDACIs) in the treatment of renal cell carcinoma (RCC). METHODS: PubMed, EMBASE, the Cochrane Library, CNKI, and the Wanfang database were searched to retrieve studies describing the use of HDACIs for the treatment of RCC published between January 1, 2009, and January 1, 2021. Relevant studies were selected, and data were extracted. Then, a meta-analysis was performed using R 3.5.2 software. RESULTS: The results showed that the objective response rate (ORR) of HDACIs used to treat RCC was 26% [95% confidence interval (95% CI): 0.19∼0.34] and that the 1-year progression-free survival (PFS) rate was 29% (95% CI: 0.14∼0.59). The ORR and PFS rate of the combination group were better than those of the monotherapy group, and the ORR and PFS rate of the selective HDACI group were better than those of the pan-HDACI group. The incidences of neutropenia and thrombocytopenia were higher and the incidence of fatigue was lower in the selective HDACI group than in the pan-HDACI group. CONCLUSION: This study initially confirmed the efficacy and safety of HDACIs for the treatment of RCC. Due to the limitations of the included studies, more high-quality studies are needed to validate the conclusions.


Assuntos
Inibidores de Histona Desacetilases/farmacologia , Antineoplásicos/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Estadiamento de Neoplasias , Resultado do Tratamento
12.
J Transl Med ; 19(1): 328, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344414

RESUMO

BACKGROUND: Severe immune-related Adverse Events (irAEs) develop in 10-27% of patients treated with Immune-Oncology (IO) [Powles (Lancet 391:748-757, 2018); Galsky (Lancet 395:1547-1557, 2020); Haanen (Ann Oncol 28:119-142, 2017)]. The aim of our study was to evaluate efficacy and clinical outcome of metastatic renal cell carcinoma (mRCC) patients who stopped Immune Checkpoint Inhibitors (ICIs) due to early Grade (G) 3-G4 irAEs. METHODS: We retrospectively collected data from 204 mRCC patients treated with ICIs in 6 Italian referral centers adhering to the Meet-Uro group, between February 2017 and January 2020. To properly weight the results, patients who did not report early G3-G4 toxicities have been included as control group. Primary endpoint was to evaluate 6 months Progression Free Survival (PFS) after early treatment interruption for Grade (G) 3-4 toxicities compared to the control group. Secondary endpoints were to evaluate Time to treatment failure (TTF) and overall survival (OS) in both groups. All statistical analyses were performed using SPSS software (version 19.00, SPSS, Chicago). RESULTS: 18/204 (8.8%) patients had early treatment interruption for serious (G3-G4) irAEs. Early was defined as interruption of IO after only one or two administrations. Immune related nephritis and pancreatitis were the most common irAE that lead to treatment interruption. 6/18 patients received IO-IO combination whereas 12/18 patients antiPD1. In the study group, 12/18 (66.6%) were free from progression at 6 months since IO interruption, TTF was 1.6 months (95% CI 1.6-2.1), mPFS was 7.4 months (95% CI 3.16-11.6) and mOS was 15.5 months (5.1-25.8). In the control group 111/184 (60.3%) patients were free from progression at 6 months, TTF was 4.6 months (95% CI 3.5-5.6), mPFS was 4.6 months (95% CI 3.5-5.6) and mOS was 19.6 months (95% CI 15.1-24.0). In the overall population, mPFS was 5.0 months (95% CI 4.0-5.9) and mOS was 19.6 months (95% CI 15.1-24.0). CONCLUSIONS: ICIs seem to maintain efficacy even after early interruption due to severe irAE.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Imunoterapia/efeitos adversos , Itália , Neoplasias Renais/tratamento farmacológico , Estudos Retrospectivos
13.
N Engl J Med ; 385(8): 683-694, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34407342

RESUMO

BACKGROUND: Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence. METHODS: In a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year). The primary end point was disease-free survival according to the investigator's assessment. Overall survival was a key secondary end point. Safety was a secondary end point. RESULTS: A total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval [CI], 0.53 to 0.87; P = 0.002 [two-sided]). The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96). Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred. CONCLUSIONS: Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nefrectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Quimioterapia Adjuvante/efeitos adversos , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Análise de Intenção de Tratamento , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva , Análise de Sobrevida
14.
Oncoimmunology ; 10(1): 1933332, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262797

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common kidney malignancy characterized by a poor prognosis. The treatment efficacy of immune checkpoint inhibitors (ICIs) also varies widely in advanced ccRCC. We aim to construct a robust gene signature to improve the prognostic discrimination and prediction of ICIs for ccRCC patients. In this study, adopting differentially expressed genes from seven ccRCC datasets in GEO (Gene Expression Omnibus), a novel signature (FOXM1&TOP2A) was constructed in TCGA (The Cancer Genome Atlas) database by LASSO and Cox regression. Survival and time-dependent ROC analysis revealed the strong predictive ability of our signature in discovery set, two online validation sets and one tissue microarray (TMA) from our institution. High-risk group based on the signature comprises more high-grade (G3&G4) and advanced pathologic stage (stageIII/IV) tumors and presents hyperactivation of cell cycle process according to the functional analysis. Meanwhile, high-risk tumors demonstrate an immunosuppressive phenotype with more infiltrations of regulatory T cells (Tregs), macrophages and high expressions of genes negatively regulating anti-tumor immunity. Low-risk tumors have an improved response to anti-PD-1 therapy and the predictive ability of our signature is better than other recognized biomarkers in ccRCC. A nomogram containing this signature showed a high predictive accuracy with AUCs of 0.90 and 0.84 at 3 and 5 years. Overall, this robust signature could predict prognosis, evaluate immune microenvironment and response to anti-PD-1 therapy in ccRCC, which is very promising in clinical promotion.


Assuntos
Carcinoma de Células Renais , Inibidores de Checkpoint Imunológico , Neoplasias Renais , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/tratamento farmacológico , Prognóstico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/genética , Microambiente Tumoral
15.
J Med Econ ; 24(1): 893-899, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34259119

RESUMO

Aims: The aim of this study was to estimate the cost-effectiveness of nivolumab versus everolimus for second-line treatment of renal cell carcinoma (RCC) based on mature data, updated safety and decreased everolimus price.Materials and methods: A 3-state (pre-progression/progression-free disease, progressive disease and death) Markov model was developed from the perspective of the Australian health care system. Two scenarios were tested. Scenario 1 used 30-months clinical data and scenario 2 used updated 80-months clinical data with updated everolimus price. Inputs for quality-of-life and costs were informed by the literature and government sources. Incremental cost-effectiveness ratio (ICER) per quality adjusted life years (QALY) gained was reported and an ICER threshold of AU$75,000 was assumed. Threshold analysis was performed, and uncertainty was explored using one-way and probabilistic sensitivity analyses.Results: In scenario 1, the model estimated 1.73 QALYs at a cost of AU$105,000 for nivolumab and 1.48 QALYs at AU$38,000 for everolimus with an ICER = AU$266,871/QALY gained. A rebate of 54.4% was needed for nivolumab to reach the ICER threshold. For scenario 2, 1.93 QALYs at AU$111,418 was estimated for nivolumab and 1.60 QALYs at AU$31,942 for everolimus with an ICER of AU$213,320/QALY gained. The rebate needed to reach the ICER threshold was 54.9%. One-way sensitivity analyses for both scenarios showed that the cost of nivolumab, time horizon and utilities were main drivers. The cost-effectiveness acceptability curves highlighted the differences in cost-effectiveness of the two scenarios, as well as significant uncertainty in the results.Conclusions: A 54% rebate of the published price is needed for nivolumab to be cost-effective in Australia for the treatment of RCC. At that rebate, nivolumab remains cost-effective despite severe price erosion of everolimus because of improved longer term follow-up data. We recommend that generic price erosion should be accounted for when performing cost-effectiveness analysis.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Austrália , Carcinoma de Células Renais/tratamento farmacológico , Análise Custo-Benefício , Humanos , Inibidores de Checkpoint Imunológico/economia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/economia , Nivolumabe/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida
18.
Int J Mol Sci ; 22(12)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207825

RESUMO

Non-clear cell renal cell carcinomas are a miscellaneous group of tumors that include different histological subtypes, each one characterized by peculiarity in terms of genetic alteration, clinical behavior, prognosis, and treatment response. Because of their low incidence and poor enrollment in clinical trials, alongside their heterogeneity, additional efforts are required to better unveil the pathogenetic mechanisms and, consequently, to improve the treatment algorithm. Nowadays, tyrosine kinase inhibitors, mTOR and MET inhibitors, and even cisplatin-based chemotherapy and immunotherapy are potential weapons that are still under evaluation in this setting. Various biomarkers have been evaluated for detecting progression and monitoring renal cell carcinoma, but more studies are necessary to improve this field. In this review, we provide an overview on the molecular characteristics of this group of tumors and the recently published trials, giving an insight into what might become the future therapeutic standard in this complex world of non-clear cell kidney cancers.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Neoplasias Renais , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-met , Serina-Treonina Quinases TOR , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo
19.
Intern Med J ; 51(7): 1173-1177, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34278692

RESUMO

The availability of efficacious systemic therapies for metastatic clear cell renal cell carcinoma has heralded improved survival for Australians. The Pharmaceutical Benefits Schedule registry was interrogated to assess nation-wide prescribing patterns. Sunitinib remained the most commonly prescribed agent. Prescribing rates were significantly lower in Northern Territory than in other states, raising questions of disparities in access to care.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/epidemiologia , Hábitos , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/epidemiologia , Northern Territory , Pirróis , Sunitinibe/uso terapêutico
20.
Photodiagnosis Photodyn Ther ; 35: 102427, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34216806

RESUMO

BACKGROUND: Photodynamic therapy is a clinically approved, minimally invasive,therapeutic procedure used for the treatment of several cancers. In recent years, sunitinib, one of the tyrosine kinase inhibitors, has also attracted attention as a novel photosensitizer. However, there is currently no data available on the combined cytotoxic effects of sunitinib and photoirradiation on renal cell carcinoma including how the treatment induced cellular toxicity. METHODS: In the present study, we used sunitinib as a photosensitizer and evaluated the effects of sunitinib and photodynamic therapy treatment on renal cancer cell lines, including the induction of cell death. RESULTS: Our study showed that treatment with sunitinib and photoirradiation at 8 mW/cm2 for 30 min resulted in the production intracellular reactive oxygen species (ROS), which is indicated by the increase in mRNA expression levels of PAI-1, NF-κß, and Caspase-3. An increase in rate of apoptotic reaction and increase in the expression level of apoptotic marker were also observed when cells undergo treatment with sunitinib and photoirradiation. CONCLUSIONS: Our findings suggest that combining photodynamic therapy with sunitinib represents a minimally invasive therapeutic procedure with cancer selectivity for renal cell carcinoma.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Fotoquimioterapia , Apoptose , Carcinoma de Células Renais/tratamento farmacológico , Linhagem Celular Tumoral , Humanos , Neoplasias Renais/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio , Sunitinibe/farmacologia
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