Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 120
Filtrar
1.
Oncologist ; 28(5): 433-439, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-36640141

RESUMO

BACKGROUND: There remains a paucity of data regarding the efficacy of immune checkpoint therapy (ICT) combinations ± vascular endothelial growth factor (VEGF) targeted therapy (TT) in translocation renal cell carcinoma (tRCC). METHODS: This is a retrospective study of patients with advanced tRCC treated with ICT combinations at 11 centers in the US, France, and Belgium. Only cases with confirmed fluorescence in situ hybridization (FISH) were included. Objective response rates (ORR) and progression-free survival (PFS) were assessed by RECIST, and overall survival (OS) was estimated by Kaplan-Meier methods. RESULTS: There were 29 patients identified with median age of 38 (21-70) years, and F:M ratio 0.9:1. FISH revealed TFE3 and TFEB translocations in 22 and 7 patients, respectively. Dual ICT and ICT + VEGF TT were used in 18 and 11 patients, respectively. Seventeen (59%) patients received ICT combinations as first-line therapy. ORR was 1/18 (5.5%) for dual ICT and 4/11 (36%) for ICT + VEGF TT. At a median follow-up of 12.9 months, median PFS was 2.8 and 5.4 months in the dual ICT and ICT + VEGF TT groups, respectively. Median OS from metastatic disease was 17.8 and 30.7 months in the dual ICT and ICT + VEGF TT groups, respectively. CONCLUSION: In this retrospective study of advanced tRCC, limited response and survival were seen after frontline dual ICT combination therapy, while ICT + VEGF TT therapy offered some efficacy. Due to the heterogeneity of tRCC, insights into the biological underpinnings are necessary to develop more effective therapies.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Fator A de Crescimento do Endotélio Vascular/genética , Estudos Retrospectivos , Hibridização in Situ Fluorescente
2.
World J Urol ; 41(4): 1069-1075, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36929410

RESUMO

PURPOSE: To describe the incidence, management, and survival outcomes of patients with muscle-invasive urothelial carcinoma (MIUC) undergoing radical surgery (RS) in France. METHODS: We relied on a non-interventional real-world retrospective study based on French National Hospitalization Database. Adults with MIUC with a first RS between 2015 and 2020 were selected. Subpopulations of patients with RS performed in 2015 and 2019 (pre-COVID-19) were extracted, according to cancer site: muscle-invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (UTUC). Disease-free and overall survival (DFS, OS - Kaplan-Meier) were assessed on the 2015 subpopulation. RESULTS: Between 2015 and 2020, 21,295 MIUC patients underwent a first RS. Of them, 68.9% had MIBC, 28.9% UTUC, and 2.2% both cancers. Apart from fewer men among UTUC (70.2%) than MIBC patients (90.1%), patients' demographic (mean age ~ 73 years) and clinical characteristics were similar whatever the cancer site or year of first RS. In 2019, RS alone was the most frequent treatment, occurring in 72.3% and 92.6% in MIBC and UTUC, respectively. Between 2015 and 2019, neoadjuvant use rate increased from 13.8% to 22.2% in MIBC, and adjuvant use rate increased from 3.7% to 6.3% in UTUC. Finally, median [95% confidence interval] DFS times were 16.0 [14.0-18.0] and 27.0 [23.0-32.0] months among MIBC and UTUC, respectively. CONCLUSION: Among patients with resected MIUC annually, RS alone remained the main treatment. Neoadjuvant and adjuvant use increased between 2015 and 2019. Nonetheless, MIUC remains of poor prognosis, highlighting an unmet medical need, notably among patients at high risk of recurrence.


Assuntos
COVID-19 , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Masculino , Adulto , Humanos , Idoso , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/patologia , Estudos Retrospectivos , Músculos
3.
Oncologist ; 27(12): 1041-1047, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-35979929

RESUMO

BACKGROUND: MiT family translocation renal cell carcinoma (TRCC) is a rare and aggressive subgroup of renal cell carcinoma harboring high expression of c-MET. While TRCC response rates to VEGF receptor tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors are limited, efficacy of cabozantinib (a VEGFR, MET, and AXL inhibitor) in this subgroup is unclear. METHODS: We performed a multicenter, retrospective, international cohort study of patients with TRCC treated with cabozantinib. The main objectives were to estimate response rate according to RECIST 1.1 and to analyze progression-free survival (PFS) and overall survival (OS). RESULTS: Fifty-two patients with metastatic TRCC treated in the participating centers and evaluable for response were included. Median age at metastatic diagnosis was 40 years (IQR 28.5-53). Patients' IMDC risk groups at diagnosis were favorable (9/52), intermediate (35/52), and poor (8/52). Eleven (21.2%) patients received cabozantinib as frontline therapy, 15 (28.8%) at second line, and 26 (50%) at third line and beyond. The proportion of patients who achieved an objective response was 17.3%, including 2 complete responses and 7 partial responses. For 26 (50%) patients, stable disease was the best response. With a median follow-up of 25.1 months (IQR 12.6-39), median PFS was 6.8 months (95%CI 4.6-16.3) and median OS was 18.3 months (95%CI 17.0-30.6). No difference of response was identified according to fusion transcript features. CONCLUSION: This real-world study provides evidence of the activity of cabozantinib in TRCC, with more durable responses than those observed historically with other VEGFR-TKIs or ICIs.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Adulto , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Estudos de Coortes , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Estudos Retrospectivos
4.
N Engl J Med ; 380(12): 1103-1115, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-30779531

RESUMO

BACKGROUND: In a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously untreated patients with advanced renal-cell carcinoma compared avelumab plus axitinib with the standard-of-care sunitinib. METHODS: We randomly assigned patients in a 1:1 ratio to receive avelumab (10 mg per kilogram of body weight) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were progression-free survival and overall survival among patients with programmed death ligand 1 (PD-L1)-positive tumors. A key secondary end point was progression-free survival in the overall population; other end points included objective response and safety. RESULTS: A total of 886 patients were assigned to receive avelumab plus axitinib (442 patients) or sunitinib (444 patients). Among the 560 patients with PD-L1-positive tumors (63.2%), the median progression-free survival was 13.8 months with avelumab plus axitinib, as compared with 7.2 months with sunitinib (hazard ratio for disease progression or death, 0.61; 95% confidence interval [CI], 0.47 to 0.79; P<0.001); in the overall population, the median progression-free survival was 13.8 months, as compared with 8.4 months (hazard ratio, 0.69; 95% CI, 0.56 to 0.84; P<0.001). Among the patients with PD-L1-positive tumors, the objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib; at a median follow-up for overall survival of 11.6 months and 10.7 months in the two groups, 37 patients and 44 patients had died, respectively. Adverse events during treatment occurred in 99.5% of patients in the avelumab-plus-axitinib group and in 99.3% of patients in the sunitinib group; these events were grade 3 or higher in 71.2% and 71.5% of the patients in the respective groups. CONCLUSIONS: Progression-free survival was significantly longer with avelumab plus axitinib than with sunitinib among patients who received these agents as first-line treatment for advanced renal-cell carcinoma. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Renal 101 ClinicalTrials.gov number, NCT02684006.).


Assuntos
Anticorpos Monoclonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Axitinibe/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Sunitinibe/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Axitinibe/efeitos adversos , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Método Simples-Cego , Sunitinibe/efeitos adversos , Taxa de Sobrevida
5.
Mol Cancer ; 20(1): 136, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670568

RESUMO

BACKGROUND: Renal Cell Carcinoma (RCC) is difficult to treat with 5-year survival rate of 10% in metastatic patients. Main reasons of therapy failure are lack of validated biomarkers and scarce knowledge of the biological processes occurring during RCC progression. Thus, the investigation of mechanisms regulating RCC progression is fundamental to improve RCC therapy. METHODS: In order to identify molecular markers and gene processes involved in the steps of RCC progression, we generated several cell lines of higher aggressiveness by serially passaging mouse renal cancer RENCA cells in mice and, concomitantly, performed functional genomics analysis of the cells. Multiple cell lines depicting the major steps of tumor progression (including primary tumor growth, survival in the blood circulation and metastatic spread) were generated and analyzed by large-scale transcriptome, genome and methylome analyses. Furthermore, we performed clinical correlations of our datasets. Finally we conducted a computational analysis for predicting the time to relapse based on our molecular data. RESULTS: Through in vivo passaging, RENCA cells showed increased aggressiveness by reducing mice survival, enhancing primary tumor growth and lung metastases formation. In addition, transcriptome and methylome analyses showed distinct clustering of the cell lines without genomic variation. Distinct signatures of tumor aggressiveness were revealed and validated in different patient cohorts. In particular, we identified SAA2 and CFB as soluble prognostic and predictive biomarkers of the therapeutic response. Machine learning and mathematical modeling confirmed the importance of CFB and SAA2 together, which had the highest impact on distant metastasis-free survival. From these data sets, a computational model predicting tumor progression and relapse was developed and validated. These results are of great translational significance. CONCLUSION: A combination of experimental and mathematical modeling was able to generate meaningful data for the prediction of the clinical evolution of RCC.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/metabolismo , Suscetibilidade a Doenças , Neoplasias Renais/etiologia , Neoplasias Renais/metabolismo , Modelos Biológicos , Animais , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/terapia , Linhagem Celular Tumoral , Biologia Computacional/métodos , Gerenciamento Clínico , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Ontologia Genética , Genômica/métodos , Xenoenxertos , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Camundongos , Prognóstico
6.
J Neurooncol ; 153(1): 133-141, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33837880

RESUMO

PURPOSE: Brain metastases (BM) usually represent a poor prognostic factor in solid tumors. About 10% of patients with renal cancer (RCC) will present BM. Local therapies such as stereotactic radiotherapy (SRT), whole brain radiotherapy (WBRT), and surgery are used to achieve brain control. We compared survival between patients with synchronous BM (SynBM group) and metachronous BM (MetaBM group). METHODS: It is a retrospective study of patients with clear cell renal cell carcinoma (ccRCC) and BM treated with TKI between 2005 and 2019 at the Centre Léon Bérard in Lyon. We collected prognostic factors: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, the TNM stage, the histological subtypes and the Fuhrman grade. Overall survival (OS) was defined from diagnosis of metastatic ccRCC to death. Brain progression-free survival (B-PFS) was defined from focal brain therapy to brain progression or death. RESULTS: 99 patients were analyzed, 44 in the SynBM group and 55 in the MetaBM group. OS in the MetaBM group was 49.4 months versus 19.6 months in the SynBM group, p = 0.0002. The median time from diagnosis of metastasic disease to apparition of BM in the MetaBM group was 22.9 months (4.3; 125.7). SRT was used for 101 lesions (66.4%), WBRT for 25 patients (16.4%), surgery for 21 lesions (13.8%), surgery followed by radiation for 5 lesions (3.3%). B-PFS for all patients was 7 months (IC95% [5.0-10.5]). CONCLUSIONS: Survival of patients with synchronous BM is inferior to that of patients with metachronous BM. Outcome is poor in both cases after diagnosis of BM. Brain screening should be encouraged at time of diagnosis of metastatis in ccRCC.


Assuntos
Neoplasias Encefálicas , Carcinoma de Células Renais , Neoplasias Renais , Encéfalo , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Carcinoma de Células Renais/terapia , Humanos , Neoplasias Renais/terapia , Prognóstico , Estudos Retrospectivos
7.
Br J Cancer ; 118(9): 1179-1188, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29563634

RESUMO

BACKGROUND: Vascular endothelial (VE)-cadherin is an endothelial cell-specific protein responsible for endothelium integrity. Its adhesive properties are regulated by post-translational processing, such as tyrosine phosphorylation at site Y685 in its cytoplasmic domain, and cleavage of its extracellular domain (sVE). In hormone-refractory metastatic breast cancer, we recently demonstrated that sVE levels correlate to poor survival. In the present study, we determine whether kidney cancer therapies had an effect on VE-cadherin structural modifications and their clinical interest to monitor patient outcome. METHODS: The effects of kidney cancer biotherapies were tested on an endothelial monolayer model mimicking the endothelium lining blood vessels and on a homotypic and heterotypic 3D cell model mimicking tumour growth. sVE was quantified by ELISA in renal cell carcinoma patients initiating sunitinib (48 patients) or bevacizumab (83 patients) in the first-line metastatic setting (SUVEGIL and TORAVA trials). RESULTS: Human VE-cadherin is a direct target for sunitinib which inhibits its VEGF-induced phosphorylation and cleavage on endothelial monolayer and endothelial cell migration in the 3D model. The tumour cell environment modulates VE-cadherin functions through MMPs and VEGF. We demonstrate the presence of soluble VE-cadherin in the sera of mRCC patients (n = 131) which level at baseline, is higher than in a healthy donor group (n = 96). Analysis of sVE level after 4 weeks of treatment showed that a decrease in sVE level discriminates the responders vs. non-responders to sunitinib, but not bevacizumab. CONCLUSIONS: These data highlight the interest for the sVE bioassay in future follow-up of cancer patients treated with targeted therapies such as tyrosine-kinase inhibitors.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Farmacológicos , Caderinas/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Sunitinibe/uso terapêutico , Biomarcadores Farmacológicos/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Células Cultivadas , Ensaios Clínicos como Assunto , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Terapia de Alvo Molecular/métodos , Metástase Neoplásica , Estudos Retrospectivos , Resultado do Tratamento
8.
BMC Cancer ; 18(1): 1271, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30567533

RESUMO

BACKGROUND: In the absence of head-to-head trials comparing axitinib with cabozantinib or everolimus, the aim of this study was to conduct an indirect comparison of their relative efficacy in patients with metastatic renal cell carcinoma (mRCC), using data from the AXIS and METEOR trials. METHODS: Progression-free survival (PFS) and overall survival (OS) in prior sunitinib-treated patients with mRCC were compared by conducting matching-adjusted indirect comparison (MAIC) analyses, including base-case and sensitivity analyses. Individual patient-level data from prior sunitinib-treated patients who received axitinib in AXIS were weighted to match published baseline characteristics of prior sunitinib-treated patients who received either cabozantinib or everolimus in METEOR. RESULTS: There was no statistically significant difference in PFS (aHR [adjusted hazard ratio] = 1.15 [CI: 0.82-1.63]) and OS (aHR = 1.00 [CI: 0.69-1.46]) between axitinib versus cabozantinib in the base-case analysis. In the sensitivity analysis, PFS (aHR = 1.39 [CI: 1.00-1.92]) and OS (aHR = 1.35 [CI: 0.95-1.92]) were shorter for axitinib compared with cabozantinib; however, the OS difference was not statistically significant. Axitinib was associated with significantly longer PFS compared with everolimus in the base-case (aHR = 0.53 [CI: 0.36-0.80]) and sensitivity analyses (aHR = 0.63 [CI: 0.45-0.88]), respectively. Results suggested an OS benefit for axitinib versus everolimus in base-case analyses (aHR = 0.63 [CI: 0.42-0.96]); however, the difference in OS in the sensitivity analysis was not statistically significant (aHR = 0.84 [CI: 0.59-1.18]). CONCLUSIONS: MAIC analyses suggest PFS and OS for axitinib and cabozantinib are dependent on the Memorial Sloan Kettering Cancer Center definition used; in the base-case analysis, there was no significant difference in PFS and OS between axitinib and cabozantinib. In the sensitivity analysis, PFS in favour of cabozantinib was significant; however, the trend for prolonged OS with cabozantinib was not significant. For axitinib and everolimus, MAIC analyses indicate patients treated with axitinib may have an improved PFS and OS benefit when compared to everolimus. Disparities between the base-case and sensitivity analyses in this study underscore the importance of adjusting for the differences in baseline characteristics and that naïve indirect comparisons are not appropriate.


Assuntos
Anilidas/uso terapêutico , Axitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Everolimo/uso terapêutico , Piridinas/uso terapêutico , Adulto , Idoso , Anilidas/efeitos adversos , Axitinibe/efeitos adversos , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Everolimo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Piridinas/efeitos adversos , Sunitinibe/efeitos adversos , Sunitinibe/uso terapêutico
9.
Future Oncol ; 14(9): 861-875, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29264944

RESUMO

Axitinib is a potent, selective, vascular endothelial growth factor receptor inhibitor with demonstrated efficacy as second-line treatment for metastatic renal cell carcinoma. Analyses of axitinib drug exposures have demonstrated high interpatient variability in patients receiving the 5 mg twice-daily (b.i.d.) starting dose. Clinical criteria can be used to assess whether individual patients may benefit further from dose modifications, based on their safety and tolerability data. This review provides practical guidance on the 'flexible dosing' method, to help physicians identify who would benefit from dose escalations, dose reductions or continuation with manageable toxicity at the 5 mg b.i.d. dose. This flexible approach allows patients to achieve the best possible outcomes without compromising safety.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Imidazóis/uso terapêutico , Indazóis/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/genética , Axitinibe , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Humanos , Imidazóis/efeitos adversos , Indazóis/efeitos adversos , Estimativa de Kaplan-Meier , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
10.
Br J Cancer ; 117(7): 947-953, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-28850564

RESUMO

BACKGROUND: Sunitinib is one of the first-line standard treatments for metastatic clear cell renal cell carcinoma (ccRCC) with a median time to progression shorter than 1 year. The objective is to discover predictive markers of response to adapt the treatment at diagnosis. METHODS: Prospective phase 2 multi-centre trials were conducted in ccRCC patients initiating sunitinib (54 patients) or bevacizumab (45 patients) in the first-line metastatic setting (SUVEGIL and TORAVA trials). The plasmatic level of CXCL7 at baseline was correlated with progression-free survival (PFS). RESULTS: The cut-off value of CXCL7 for PFS was 250 ng ml-1. Patients with CXCL7 plasmatic levels above the cut-off at baseline (250 ng ml-1) had a significantly longer PFS (hazard ratio 0.323 (95% confidence interval 0.147-0.707), P=0.001). These results were confirmed in a retrospective validation cohort. The levels of CXCL7 did not influence PFS of the bevacizumab-treated patients. CONCLUSIONS: CXCL7 may be considered as a predictive marker of sunitinib efficacy for ccRCC patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Renais/sangue , Neoplasias Renais/tratamento farmacológico , Pirróis/uso terapêutico , beta-Tromboglobulina/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Biomarcadores Tumorais/sangue , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Células Matadoras Naturais , Linfócitos do Interstício Tumoral , Macrófagos , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Transplante de Neoplasias , Nefrectomia , Neutrófilos , Estudos Prospectivos , Estudos Retrospectivos , Sirolimo/administração & dosagem , Sirolimo/análogos & derivados , Sunitinibe , Taxa de Sobrevida
11.
BMC Cancer ; 17(1): 547, 2017 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-28810837

RESUMO

BACKGROUND: Vascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors. METHODS: In this bicentric phase I trial with a 3 + 3 + 3 dose-escalation design, patients received oral pazopanib once daily plus intravenous infusion of bevacizumab every 2 weeks from D15, at one of the four dose levels (DL) planned according to the occurrence of dose limiting toxicities (DLT). 400 and 600 mg pazopanib were respectively combined with 7.5 mg/kg bevacizumab in DL1 and DL2, and 600 and 800 mg pazopanib with 10 mg/kg bevacizumab in DL3 and DL4. Tumor response was evaluated every 8 weeks. Blood samples were assayed to investigate pazopanib pharmacokinetics. RESULTS: Twenty five patients including seven mRCC were enrolled. Nine patients received the DL1, ten received the DL2. No DLT were observed at DL1, five DLT at DL2, and 3 DLT in the six additional patients who received the DL1. A grade 3 microangiopathic hemolytic anemia syndrome was observed in four (16%) patients. Five (22%) patients achieved a partial response. The mean (range) plasmatic concentrations of 400 and 600 pazopanib were respectively 283 (139-427) and 494 (227-761) µg.h/mL at Day 1, and 738 (487-989) and 1071 (678-1464) µg.h/mL at Day 15 i.e. higher than those previously reported with pazopanib, and were not directly influenced by bevacizumab infusion. CONCLUSIONS: The combination of pazopanib and bevacizumab induces angiogenic toxicity in patients without any pre-existing renal or vascular damage. Even if a marginal efficacy was reported with five (22%) patients in partial response in different tumor types, the toxicity profile compromises the development of this combination. TRIAL REGISTRATION: The study was retrospectively registered on ClinicalTrials.gov (number NCT01202032 ) on 2010, Sept 14th.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Carcinoma de Células Renais/mortalidade , Terapia Combinada , Monitoramento de Medicamentos , Feminino , Humanos , Indazóis , Neoplasias Renais/mortalidade , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Resultado do Tratamento
12.
Invest New Drugs ; 34(1): 41-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26572909

RESUMO

INTRODUCTION: Pazopanib exhibits wide inter-patient pharmacokinetic variability which may contribute to differences in treatment outcome. Unbound drug concentrations are believed to be more relevant to pharmacological responses than total concentrations. Thus it is desirable to evaluate pazopanib binding on plasma proteins and different factors potentially affecting this process. METHODS: An equilibrium dialysis method coupled with UPLC-MS/MS assay has been optimized and validated for the determination of pazopanib unbound fraction (fu%) in human plasma. Pazopanib binding in the plasma of healthy volunteers and in isolated protein solutions was investigated. The unbound fraction was determined for 24 cancer patients treated daily with pazopanib. RESULTS: We found that pazopanib was extensively bound in human plasma (>99.9 %) with a mean fu% value of 0.0106 ± 0.0013 % at 40 µg/mL. Protein binding was concentration independent over a clinically relevant range of concentrations. In isolated protein solutions, pazopanib at 40 µg/mL was mainly bound to albumin (40 g/L) and to a lesser extent to α1-acid glycoprotein (1 g/L) and low density lipoproteins (1.2 g/L), with a mean fu% of 0.0073 ± 0.0022 %, 0.992 ± 0.44 % and 7.4 ± 1.7 % respectively. Inter-patient variability (CV%) of fu% in cancer patients was limited (27.2 %). A correlation was observed between individual unbound fraction values and albuminemia. CONCLUSIONS: Pazopanib exhibits extensive binding to plasma proteins in human plasma. Variable albumin concentrations, frequently observed in cancer patients, may affect pazopanib unbound fraction with implications for inter-patient variability in drug efficacy and toxicity.


Assuntos
Antineoplásicos/farmacocinética , Neoplasias/metabolismo , Pirimidinas/farmacocinética , Albumina Sérica/metabolismo , Sulfonamidas/farmacocinética , Antineoplásicos/uso terapêutico , Sítios de Ligação , Proteínas Sanguíneas/metabolismo , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Técnicas In Vitro , Indazóis , Neoplasias/tratamento farmacológico , Ligação Proteica , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Espectrometria de Massas em Tandem/métodos
13.
Anticancer Drugs ; 27(5): 427-32, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27045782

RESUMO

Molecular targeted therapies (TT) are the cornerstone of metastatic renal cell carcinoma (RCC) treatment. There is a paucity of data on the safety of the radiotherapy (RT)-TT association in a sequential or a concomitant setting. The aim of the present study is to retrospectively assess the safety of the RT-TT association. From 2006 to 2014, data from 84 consecutive patients treated with RT and TT for metastatic RCC were retrospectively collected. RT-TT sequential and concomitant associations were, respectively, defined by a time interval of more than five TT half-lives and less than or equal to five TT half-lives between the last TT administration and RT initiation. Toxicities in the fields of RT were assessed systematically. As many patients received several TT and RT courses, 136 RT-TT associations were analyzed, with 66 sequential and 70 concomitant schemes. RT was mainly delivered on bone (75%) and brain metastases (14.7%). TT were tyrosine kinase inhibitors (73.5%), mTOR inhibitors (19.8%), and monoclonal antibodies (6.7%). With a median follow-up of 9.5 months, whatever the sequence, no grade≥4 toxicity was reported. Two grade 3 toxicities were reported with sequential (3%) and concomitant (2.9%) RT-TT, respectively. Sequential or concomitant RT-TT associations in metastatic RCC do not seem to cause major toxicity.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Carcinoma de Células Renais/secundário , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Proteínas Tirosina Quinases/antagonistas & inibidores , Estudos Retrospectivos , Serina-Treonina Quinases TOR/antagonistas & inibidores
14.
Br J Cancer ; 113(8): 1148-57, 2015 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-26372698

RESUMO

BACKGROUND: Renal cell carcinoma is one of the most chemoresistant cancers, and its metastatic form requires administration of targeted therapies based on angiogenesis or mTOR inhibitors. Understanding how these treatments impact the human metabolism is essential to predict the host response and adjust personalised therapies. We present a metabolomic investigation of serum samples from patients with metastatic RCC (mRCC) to identify metabolic signatures associated with targeted therapies. METHODS: Pre-treatment and serial on-treatment sera were available for 121 patients participating in the French clinical trial TORAVA, in which 171 randomised patients with mRCC received a bevacizumab and temsirolimus combination (experimental arm A) or a standard treatment: either sunitinib (B) or interferon-α+bevacizumab (C). Metabolic profiles were obtained using nuclear magnetic resonance spectroscopy and compared on-treatment or between treatments. RESULTS: Multivariate statistical modelling discriminates serum profiles before and after several weeks of treatment for arms A and C. The combination A causes faster changes in patient metabolism than treatment C, detectable after only 2 weeks of treatment. Metabolites related to the discrimination include lipids and carbohydrates, consistently with the known RCC metabolism and side effects of the drugs involved. Comparison of the metabolic profiles for the three arms shows that temsirolimus, an mTOR inhibitor, is responsible for the faster host metabolism modification observed in the experimental arm. CONCLUSIONS: In mRCC, metabolomics shows a faster host metabolism modification induced by a mTOR inhibitor as compared with standard treatments. These results should be confirmed in larger cohorts and other cancer types.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Soro/metabolismo , Sirolimo/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/metabolismo , Feminino , Humanos , Indóis/uso terapêutico , Interferon-alfa/metabolismo , Neoplasias Renais/sangue , Neoplasias Renais/metabolismo , Masculino , Metaboloma/fisiologia , Pessoa de Meia-Idade , Pirróis/uso terapêutico , Sirolimo/uso terapêutico , Sunitinibe , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo
15.
Cancer ; 120(12): 1871-80, 2014 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-24634003

RESUMO

BACKGROUND: Using phase 3 trial data for sunitinib versus interferon (IFN)-α in treatment-naive patients with metastatic renal cell carcinoma, retrospective analyses characterized sunitinib-associated fatigue and its impact on patient-reported health-related quality of life (HRQoL). METHODS: Patients received sunitinib at a dose of 50 mg/day on a schedule of 4 weeks on/2 weeks off (375 patients) or IFN-α at a dose of 9 MU subcutaneously 3 times per week (360 patients). HRQoL was self-assessed using the Functional Assessment of Cancer Therapy-Kidney Symptom Index-15-item (FKSI-15) questionnaire, with fatigue assessed using its Disease-Related Symptoms subscale. Fatigue was also assessed by providers using Common Terminology Criteria for Adverse Events (CTCAE). A repeated-measures model (M1) and random intercept-slope model (M2) characterized sunitinib-associated fatigue over time. Another repeated-measures model examined the relationship between HRQoL scores and CTCAE fatigue grade. RESULTS: M1 demonstrated that the initial increase in patient-reported fatigue with sunitinib was worst during cycle 1, with mean values numerically better at subsequent cycles; most pairwise comparisons of consecutive CTCAE fatigue cycle means were not found to be statistically significant. M2 demonstrated that the overall trend (slope) for patient-reported and CTCAE fatigue with sunitinib was not statistically different from 0. The relationship between most HRQoL scores and CTCAE fatigue was close to linear regardless of treatment, with lower scores (worse HRQoL) corresponding to higher fatigue grade. The majority of HRQoL scores were better with sunitinib versus IFN-α for the same CTCAE fatigue grade. CONCLUSIONS: Patients reported worse fatigue during the first sunitinib cycle. However, in subsequent consecutive cycles, less fatigue was reported with no statistically significant worsening. CTCAE fatigue assessment may not fully capture patient treatment experience.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Fadiga/induzido quimicamente , Indóis/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Pirróis/efeitos adversos , Antineoplásicos/administração & dosagem , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/fisiopatologia , Esquema de Medicação , Fadiga/fisiopatologia , Feminino , Humanos , Indóis/administração & dosagem , Interferon-alfa/administração & dosagem , Neoplasias Renais/patologia , Neoplasias Renais/fisiopatologia , Masculino , Modelos Estatísticos , Metástase Neoplásica , Pirróis/administração & dosagem , Qualidade de Vida , Estudos Retrospectivos , Sunitinibe , Inquéritos e Questionários , Resultado do Tratamento
16.
Lancet Oncol ; 14(6): 552-62, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23598172

RESUMO

BACKGROUND: In a phase 3 trial comparing the efficacy and safety of axitinib versus sorafenib as second-line treatment for metastatic renal cell carcinoma, patients given axitinib had a longer progression-free survival (PFS). Here, we report overall survival and updated efficacy, quality of life, and safety results. METHODS: Eligible patients had clear cell metastatic renal cell carcinoma, progressive disease after one approved systemic treatment, and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1. 723 patients were stratified by ECOG PS and previous treatment and randomly allocated (1:1) to receive axitinib (5 mg twice daily; n=361) or sorafenib (400 mg twice daily; n=362). The primary endpoint was PFS assessed by a masked, independent radiology review committee. We assessed patient-reported outcomes using validated questionnaires. Baseline characteristics and development of hypertension on treatment were studied as prognostic factors. Efficacy was assessed in the intention-to-treat population, and safety was assessed in patients who received at least one dose of the study drug. This ongoing trial is registered on ClinicalTrials.gov, number NCT00678392. FINDINGS: Median overall survival was 20.1 months (95% CI 16.7-23.4) with axitinib and 19.2 months (17.5-22.3) with sorafenib (hazard ratio [HR] 0.969, 95% CI 0.800-1.174; one-sided p=0.3744). Median investigator-assessed PFS was 8.3 months (95% CI 6.7-9.2) with axitinib and 5·7 months (4.7-6.5) with sorafenib (HR 0.656, 95% CI 0.552-0.779; one-sided p<0.0001). Patient-reported outcomes scores were similar in the treatment groups at baseline, were maintained during treatment, but decreased at end-of-treatment. Common grade 3 or higher treatment-related adverse events were hypertension (60 [17%]), diarrhoea (40 [11%]), and fatigue (37 [10%]) in 359 axitinib-treated patients and hand-foot syndrome (61 [17%]), hypertension (43 [12%]), and diarrhoea (27 [8%]) in 355 sorafenib-treated patients. In a post-hoc 12-week landmark analysis, median overall survival was longer in patients with a diastolic blood pressure of 90 mm Hg or greater than in those with a diastolic blood pressure of less than 90 mm Hg: 20.7 months (95% CI 18.4-24.6) versus 12.9 months (10.1-20.4) in the axitinib group (p=0.0116), and 20.2 months (17.1-32.0) versus 14.8 months (12.0-17.7) in the sorafenib group (one-sided p=0.0020). INTERPRETATION: Although overall survival, a secondary endpoint for the study, did not differ between the two groups, investigator-assessed PFS remained longer in the axitinib group compared with the sorafenib group. These results establish axitinib as a second-line treatment option for patients with metastatic renal cell carcinoma. FUNDING: Pfizer Inc.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Imidazóis/uso terapêutico , Indazóis/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Axitinibe , Carcinoma de Células Renais/enzimologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Intervalo Livre de Doença , Feminino , Humanos , Imidazóis/efeitos adversos , Indazóis/efeitos adversos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Neoplasias Renais/enzimologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/efeitos adversos , Qualidade de Vida , Sorafenibe , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
17.
Clin Genitourin Cancer ; 22(2): 295-304.e6, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38105152

RESUMO

BACKGROUND: Treatment landscape for advanced renal cell carcinoma (aRCC) has evolved quickly and few data about the real-world treatment patterns are available. This study aimed at describing the real-world treatment patterns and effectiveness of all systemic treatments available for aRCC in first and second-line treatment. MATERIALS AND METHODS: A cohort of patients initiating a first-line systemic treatment for aRCC in 2016 was extracted from the French nationwide healthcare insurance system database (SNDS). The first-line treatment initiation date constituted the index date and patients were followed until death, loss to follow-up, or December 31, 2019, whichever occurred first. aRCC was identified using hospital diagnosis, long-term disease, or renal biopsy before index date. All analyses were performed for first and second-line treatment. Overall survival (OS) and time-to-next treatment or death (TNT-D) were estimated using Kaplan-Meier approach. RESULTS: In 2016, 1629 patients initiated a first-line treatment for aRCC. Most of them were male (75.9%) and the median age was 67 years. Most of patients (91.7%) had received a tyrosine kinase inhibitor as first-line treatment, mainly sunitinib (64.4%), and 53.5% received a second-line, among which 43.7% nivolumab. Median OS (95% confidence interval [CI]) was 20.7 (95% CI:18.2-22.4) months from first-line treatment initiation and 15.4 (13.9-17.5) months from second-line treatment initiation. Median TNT-D were respectively 9.3 (9.7-12.1) months and 6.9 (5.9-7.7) months. CONCLUSION: This study highlights the limited survival of aRCC patients These results provide a valuable baseline and highlight the need for innovation, such as immune checkpoint inhibitor-based combinations that have recently became first-line standard of care.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Masculino , Idoso , Feminino , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Resultado do Tratamento , Estudos Retrospectivos , Sunitinibe/uso terapêutico
18.
Eur J Cancer ; 201: 113589, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382153

RESUMO

INTRODUCTION: Immune checkpoint inhibitors are standard of care in metastatic renal cell carcinoma but their activity and safety in elderly patients is insufficiently explored. We evaluated outcomes of elderly patients with mRCC treated with nivolumab in the GETUG-AFU 26 NIVOREN phase 2 trial (NCT03013335) and conducted exploratory circulating biomarker analyses. METHODS: Patients with mRCC were treated with nivolumab after at least one antiangiogenic therapy. The main endpoint of this analysis was safety in patients ≥ 70 years old (y.o), as per the rate of treatment-related grade 3-5 events (TRAE). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival. Exploration of candidate biomarkers associated with aging included baseline circulating cytokines involved in inflammation, adhesion, immune checkpoints, angiogenesis (IL6, IL7, IL8, BAFF, CXCL13, VCAM-1, 4-1BB, VEGF). RESULTS: Of 720 patients, 515 were < 70 y.o and 205 ≥ 70 y.o. Patients ≥ 70 y.o exhibited numerically less IMDC poor risk disease (21.0% vs 26.9%), sarcomatoid component (4.9% vs 9.8%) or brain metastases (5.9% vs. 14.7%), but more previous treatment lines (≥ 2 in 54.1% vs 48.5%). TRAE were higher in patients ≥ 70 y.o (24.9% vs. 17.9%, p = 0.033). Respective ORR (19.2% vs. 22.1%) and median PFS (4.5 versus 3.0 months, HR 0.97 [95%CI 0.81-1.15]) were similar. Overall survival was shorter in patients ≥ 70 y.o (19.3 versus 26.9 months, HR 1.26 [95%CI 1.04-1.51]), but not significantly in a competitive risk model. Only V-CAM1 and 4-1BB were found to be increased in patients ≥ 70 y.o. CONCLUSIONS: Nivolumab displayed higher grade 3/4 TRAE but manageable toxicity in elderly patients, with sustained activity. Elderly patients did not display specific inflammatory or angiogenic circulating profiles.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Idoso , Carcinoma de Células Renais/patologia , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão
19.
Eur J Cancer ; 204: 114048, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38653033

RESUMO

BACKGROUND: The Lung Immune Prognostic Index (LIPI) is associated with immune checkpoint inhibitors (ICI) outcomes across different solid tumors, particularly in non-small cell lung cancer. Data regarding the prognostic and/or predictive role of LIPI in metastatic renal cell carcinoma (mRCC) are still scarce. The aim of this study was to evaluate whether LIPI could be predictive of survival in mRCC patients. METHODS: We used patient level data from three different prospective studies (NIVOREN trial: nivolumab; TORAVA trial: VEGF/VEGFR-targeted therapy (TT); CheckMate 214: nivolumab-ipilimumab vs sunitinib). LIPI was calculated based on a derived neutrophils/(leukocyte-neutrophil) ratio > 3 and lactate-dehydrogenase >upper limit of normal, classifying patients into three groups (LIPI good, 0 factors;LIPI intermediate (int), 1 factor;LIPI poor, 2 factors) and/or into two groups (LIPI good, 0 factors;LIPI int/poor, 1-2 factors) according to trial sample size. Primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: In the Nivolumab dataset (n = 619), LIPI was significantly associated with OS (LIPI-good 30.1 vs 13.8 months in the LIPI int/poor; HR= 0.47) and PFS (HR=0.74). In the VEGF/VEGFR-TT dataset (n = 159), only a correlation with PFS was observed. In the CheckMate214 dataset (n = 1084), LIPI was significantly associated with OS (nivolumab-ipilimumab OS LIPI good vs int/poor: HR=0.55, p < 0.0001; sunitinib: OS LIPI good vs int/poor: 0.38, p < 0.0001) in both treatment groups in univariate and multivariate analysis. CONCLUSIONS: Pretreatment-LIPI correlated with worse survival outcomes in mRCC treated with either ICI or antiangiogenic therapy, confirming LIPI's prognostic role in mRCC irrespective of systemic treatment used.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Pulmonares , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/secundário , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/imunologia , Neoplasias Renais/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Prognóstico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/imunologia , Estudos Prospectivos , Biomarcadores Tumorais/análise , Sunitinibe/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Nivolumabe/uso terapêutico , Intervalo Livre de Progressão , Adulto
20.
Clin Genitourin Cancer ; 21(2): e35-e43, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36272959

RESUMO

INTRODUCTION: Metastatic non clear cell renal cell carcinoma (nccRCC) is an heterogenous group, usually excluded from phase 3 trials. We report real life data of prognosis and systemic management of those patients. METHODS: We retrospectively included 102 metastatic nccRCC patients (unspecified papillary, n = 10; type 1 and 2 papillary n = 10 and n = 32; translocation RCC, n = 9; chromophobe, n = 14; collecting duct, n = 14) treated between 2006 and 2020. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Among patients who underwent pathological review, 40.8% presented a complete histological discordance. First line treatments were mainly tyrosine kinase inhibitor (60.8%), combination including immunotherapy (7.8%) or combination of chemotherapy (13.7%). Median ORR ranged from 0% in unspecified papillary RCC to 42.9% in type 1 papillary RCC. Median PFS ranged from 2.9 months in collecting duct carcinoma to 10.9 months in type 1 papillary RCC. Median OS ranged from 6.8 months in collecting duct carcinoma to 29.1 months in MiT family translocation RCC. Thirty (29.4%) patients were included in a treatment trial during their treatment course. CONCLUSION: Metastatic nccRCC patients have variable prognosis due to heterogeneity of histological subtypes. Their diagnosis and access to therapeutic innovation remain suboptimal. Dedicated prospective trials are needed.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Estudos Retrospectivos , Estudos Prospectivos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA