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1.
Crit Rev Oncol Hematol ; 170: 103596, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35031442

RESUMO

The primary endpoint of MOUSEION-01 was to assess overall survival (OS) in male and female patients receiving immune checkpoint inhibitors versus control treatments, calculating the pooled OS Hazard Ratio (HR) and 95 % Confidence Interval (CI) in both groups. 37 randomized phase III studies and 22646 patients (16382 men and 6264 women) were included. In patients treated with immunotherapy (as monotherapy or in combination with other agents), the pooled OS HR was 0.78 (0.75-0.82) and 0.77 (95 % CI, 0.72-0.83) in male and female subjects, respectively. The pooled HR for OS in male patients treated with single-agent immunotherapy versus control was 0.77 (95 % CI, 0.70-0.85), while this benefit was smaller in female patients (HR, 0.81; 95 % CI, 0.73-0.9). Our findings highlight that high-quality trials accounting for potential confounders are needed before being able to suggest a real effect of the patient's gender on immune checkpoint inhibitors efficacy in different settings.

2.
Target Oncol ; 2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34894318

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) represent the standard of care as first- or second-line treatment in patients with renal cell carcinoma (RCC). Proton pump inhibitors (PPIs) are among the most prescribed drugs worldwide and are known to affect gut microbiota, which is gaining interest in its association with outcomes for patients on ICIs. OBJECTIVE: The aim of this study was to evaluate the impact of PPIs on outcomes in RCC patients receiving immunotherapy. PATIENTS AND METHODS: We retrospectively collected data from patients with metastatic RCC who received the combination of ipilimumab and nivolumab for first-line treatment (Cohort 1) or single-agent nivolumab for second-line or third-line treatment (Cohort 2) from five international centers with expertise in the treatment of RCC. Data about clinicopathological characteristics, PPI use, and outcome on ICIs were collected. Endpoints of the study were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: Two hundred and eighteen patients (71% male, median age 61 years) were included in the analysis, 62 in Cohort 1 (including 25 patients receiving PPIs) and 156 in Cohort 2 (including 88 patients receiving PPIs), and were followed up for a median of 42 months. In Cohort 1, no difference was observed in ORR (48% vs 57%; p = 0.203), PFS (12.2 vs 8.5 months; p = 0.928), or OS (not reached [NR] vs 27.3 months; p = 0.84). In Cohort 2, no difference was observed in ORR (32% vs 28%; p = 0.538), PFS (6.7 vs 9.0 months; p = 0.799), or OS (16.0 vs 26.0 months; p = 0.324). CONCLUSIONS: In patients with RCC, concomitant PPI use did not seem to affect survival outcomes on ICIs, either as combination therapy or monotherapy.

3.
JCO Precis Oncol ; 52021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34476329

RESUMO

PURPOSE: Tissue-based comprehensive genomic profiling (CGP) is increasingly used for treatment selection in patients with advanced cancer; however, tissue availability may limit widespread implementation. Here, we established real-world CGP tissue availability and assessed CGP performance on consecutively received samples. MATERIALS AND METHODS: We conducted a post hoc, nonprespecified analysis of 32,048 consecutive tumor tissue samples received for StrataNGS, a multiplex polymerase chain reaction (PCR)-based comprehensive genomic profiling (PCR-CGP) test, as part of an ongoing observational trial (NCT03061305). Sample characteristics and PCR-CGP performance were assessed across all tested samples, including exception samples not meeting minimum input quality control (QC) requirements (< 20% tumor content [TC], < 2 mm2 tumor surface area [TSA], DNA or RNA yield < 1 ng/µL, or specimen age > 5 years). Tests reporting ≥ 1 prioritized alteration or meeting TC and sequencing QC were considered successful. For prostate carcinoma and lung adenocarcinoma, tests reporting ≥ 1 actionable or informative alteration or meeting TC and sequencing QC were considered actionable. RESULTS: Among 31,165 (97.2%) samples where PCR-CGP was attempted, 10.7% had < 20% TC and 59.2% were small (< 25 mm2 tumor surface area). Of 31,101 samples evaluable for input requirements, 8,089 (26.0%) were exceptions not meeting requirements. However, 94.2% of the 31,101 tested samples were successfully reported, including 80.5% of exception samples. Positive predictive value of PCR-CGP for ERBB2 amplification in exceptions and/or sequencing QC-failure breast cancer samples was 96.7%. Importantly, 84.0% of tested prostate carcinomas and 87.9% of lung adenocarcinomas yielded results informing treatment selection. CONCLUSION: Most real-world tissue samples from patients with advanced cancer desiring CGP are limited, requiring optimized CGP approaches to produce meaningful results. An optimized PCR-CGP test, coupled with an inclusive exception testing policy, delivered reportable results for > 94% of samples, potentially expanding the proportion of CGP-testable patients and impact of biomarker-guided therapies.

4.
Target Oncol ; 16(5): 625-632, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34338966

RESUMO

BACKGROUND: Renal cell carcinoma with sarcomatoid differentiation is a highly aggressive form of kidney cancer. OBJECTIVE: We aimed to analyze the outcomes of patients treated with cabozantinib for metastatic renal cell carcinoma with sarcomatoid features. METHODS: We retrospectively collected data from 16 worldwide centers. Overall survival and progression-free survival were analyzed using Kaplan-Meier curves. Cox proportional models were used for univariate and multivariate analyses. RESULTS: We collected data from 66 patients with metastatic sarcomatoid renal cell carcinoma receiving cabozantinib as second-line (51%) or third-line (49%) therapy. The median progression-free survival from the start of cabozantinib was 7.59 months (95% confidence interval [CI] 5.75-17.49) and was longer in male patients (8.81 vs 5.95 months, p = 0.042) and in patients without bone metastases (7.59 vs 5.11 months, p = 0.010); the median overall survival was 9.11 months (95% CI 7.13-23.80). At the multivariate analysis, female sex (hazard ratio = 1.81; 95% CI 1.02-3.37, p = 0.046), bone metastases (hazard ratio = 2.62; 95% CI 1.34-5.10, p = 0.005), and International Metastatic Renal Cell Carcinoma Database Consortium criteria (hazard ratio = 3.04; 95% CI 1.54-5.99, p = 0.001) were significant predictors of worse overall survival. CONCLUSIONS: Our data show that cabozantinib is active in pretreated patients with sarcomatoid renal cell carcinoma. Biomarkers are needed in this field to select patients for multi-kinase inhibitors or other options.

5.
J Immunother Cancer ; 9(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34226279

RESUMO

BACKGROUND: Corticosteroids (CS) are the mainstay of immune-related adverse effect (irAE) management, as well as for other indications in cancer treatment. Previous studies evaluating whether CS affect immune checkpoint inhibitor (CPI) efficacy compared patients receiving CS versus no CS. However, there is a paucity of clinical data evaluating the timing of concomitant CS and CPI efficacy. METHODS: We retrospectively collected data from patients who received CS during CPI treatment at a single institution. Patients were in two cohorts based on timing of initiation of CS (≥2 months vs <2 months after initiating CPI). Patient characteristics, irAEs, cancer type, treatment type, treatment response/progression per RECIST V.1.1, and survival data were collected. Kaplan-Meier and Cox proportional hazard regression methods estimated HRs for the primary endpoint of progression-free survival (PFS) along with overall survival (OS). RESULTS: We identified 247 patients with metastatic cancer who received CS concurrently with CPIs. The median time on CS was 1.8 months. After adjusting for treatment type, tumor type, brain metastases, and irAEs, those treated with CS ≥2 months after starting CPI had a statistically significant longer PFS (HR=0.30, p<0.001), and OS (HR 0.34, p<0.0001) than those who received CS <2 months after starting CPI. Objective response rate (ORR) for patients on CS ≥2 months was 39.8%, versus ORR for patients <2 months was 14.7% (p value =<0.001) CONCLUSION: Our results suggest that early use of CS during CPI treatment significantly hinders CPI efficacy. This data needs to be validated prospectively. Future studies should focus on the immune mechanisms by which CSs affect T-cell function early in the CPI treatment course.

6.
Diagnostics (Basel) ; 11(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33477676

RESUMO

We analyzed the clinical and pathological features of renal cell carcinoma (RCC) patients treated with cabozantinib stratified by body mass index (BMI). We retrospectively collected data from 16 worldwide centers involved in the treatment of RCC. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses. We collected data from 224 patients with advanced RCC receiving cabozantinib as second- (113, 5%) or third-line (111, 5%) therapy. The median PFS was significantly higher in patients with BMI ≥ 25 (9.9 vs. 7.6 months, p < 0.001). The median OS was higher in the BMI ≥ 25 subgroup (30.7 vs. 11.0 months, p = 0.003). As third-line therapy, both median PFS (9.2 months vs. 3.9 months, p = 0.029) and OS (39.4 months vs. 11.5 months, p = 0.039) were longer in patients with BMI ≥ 25. BMI was a significant predictor for both PFS and OS at multivariate analysis. We showed that a BMI ≥ 25 correlates with longer survival in patients receiving cabozantinib. BMI can be easily assessed and should be included in current prognostic criteria for advanced RCC.

7.
Clin Genitourin Cancer ; 19(2): e84-e91, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33262083

RESUMO

INTRODUCTION: The incidence of kidney cancer is increasing; it could be counteracted with new ways to predict and detect it. We aimed to implement an artificial neural network in order to predict new cases of renal-cell carcinoma (RCC) in the population using population rate, obesity, smoking incidence, uncontrolled hypertension, and life expectancy data in the United States. PATIENTS AND METHODS: Statistics were collected on US population numbers, life expectancy, obesity, smoking, and hypertension. We used MATLAB R2018 (MathWorks) software to implement an artificial neural network. Data were repeatedly and randomly divided into training (70%) and validation (30%) subsets. RESULTS: The number of new RCC cases will grow from 44,400 (2020) to 55,400 (2050), an increase of +24.7%. Our data show that preventing hypertension would have the greatest impact on reduction of the incidence, estimated at -775 and -575 cases per year in 2020 and in 2030, respectively. The prevention of obesity and smoking would have a more limited impact, estimated at -64 and -180 cases per year in 2020 and in 2030, respectively, for obesity, and -173 and -21 cases per year in 2020 and in 2030, respectively, for smoking. CONCLUSIONS: Our predictions underline the need for accurate studies on RCC-related risk factors to reduce the incidence.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/epidemiologia , Humanos , Incidência , Neoplasias Renais/epidemiologia , Redes Neurais de Computação , Fatores de Risco , Fumar , Estados Unidos/epidemiologia
8.
Urology ; 147: 186-191, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33203521

RESUMO

OBJECTIVE: To examine the rates of adverse surgical outcomes in patients undergoing cytoreductive nephrectomy (CN) compared to patients undergoing radical nephrectomy in the nonmetastatic setting using a large administrative database. METHODS: Patients in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) who underwent a radical nephrectomy between 2011 and 2016 were included. Patients were stratified by the preoperative variable of presence or absence of metastatic cancer. Perioperative outcomes were compared. A multivariable logistic regression analysis was performed to test the association between patients with metastatic cancer and perioperative morbidity and 30-day mortality. RESULTS: There were 15,869 total patients included in this analysis of whom 1322 (8%) patients had metastatic cancer. Of the entire cohort, the majority of patients were over 60 years old (58%) and 9621 (61%) were male. Seventy-three of the patients were Caucasian. Patients with metastatic cancer had more minor (P< .01) and major (P< .01) complications, a higher rate of reoperation (P< .01), and a higher rate of unplanned readmissions (P< .01). Finally, the cohort with metastatic cancer had a higher rate of postoperative 30-day mortality (P< .01) than patients without metastatic cancer. CONCLUSION: Patients undergoing a CN have significantly worse perioperative outcomes than patients undergoing a radical nephrectomy without evidence of metastases. Careful surgical risk stratification and appropriate patient counseling should be undertaken when selecting candidates for CN.

9.
Ochsner J ; 20(1): 98-103, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32284690

RESUMO

Background: Clinical research studies often integrate precision medicine technologies and techniques, offering novel treatment opportunities for patients but also posing significant challenges for regulatory authorities and local institutional review boards (IRBs) as they attempt to protect patient safety and privacy. Methods: We review the basics of precision medicine and discuss how IRBs are addressing new challenges associated with the era of precision medicine. Results: Precision medicine trials rely on genomic testing for inclusion criteria and investigational drug therapy choices. The vast amounts of complex information that can be obtained from basic genetic sequencing tests must be stored, analyzed, and interpreted, creating challenges for clinicians, researchers, and regulatory staff who are concerned with complex ethical, security, and legal issues surrounding patients' personal genetic data in the digital age. All members of the IRB face a rapidly changing environment. The traditional areas of primary concern, such as patient privacy, terminology, and financial benefits, have been joined by issues associated with precision medicine, such as accelerated US Food and Drug Administration drug approval, multiple informed consent form modifications, increasing length and complexity of informed consent forms, and participant genetic privacy. The challenge to the IRB is to remain focused on the prior areas of significance while also adapting the evaluation process to the novel science of precision medicine. Conclusion: In this era of exponentially increasing big data and easy-to-access genetic sequencing data, IRBs will be tasked with adapting their processes and adjusting to the new technology and its corresponding complexities. Such adaptation has always been required of IRBs, but now it will need to occur rapidly as technology and data analysis capabilities accelerate.

10.
Abdom Radiol (NY) ; 45(6): 1872-1882, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31822966

RESUMO

PURPOSE: To identify the optimum response criteria for first-line targeted pazopanib therapy in patients with mRCC using solid tumor response criteria and clinical risk factors. METHODS: Pre- and post-treatment CTs of patients (n = 43) with mRCC treated with first-line pazopanib therapy were analyzed retrospectively. Treatment response was evaluated with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Choi, modified Choi (mChoi), revised Choi (rChoi), MASS (Morphology, Attenuation, Size, and Structure), 10% threshold criteria, and subjective assessment. Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium clinical risk factors were also used to define response groups. Response evaluations were correlated with overall survival (OS) and progression-free survival (PFS) using log-rank test. RESULTS: Patients with partial response (PR) by mChoi and rChoi had longer OS than those with stable disease (SD) (P < 0.001). Responders by 10% threshold criteria also had better OS, without or combined with clinical criteria. Patients with PR by rChoi, mChoi, RECIST v1.1, MASS criteria, and by subjective assessment had longer PFS than those with SD. rChoi and mChoi criteria best delineated the difference in PFS for patients with PR versus SD, without or combined with clinical criteria. CONCLUSION: For mRCC patients treated with pazopanib, OS and PFS for PR and SD groups were best predicted by rChoi and mChoi criteria, without or combined with clinical risk factors. 10% threshold criteria also predicted OS and PFS, whereas RECIST did so only in a limited number of patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Indazóis , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Sulfonamidas , Resultado do Tratamento
11.
Cancers (Basel) ; 12(1)2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31905816

RESUMO

Cabozantinib is approved for the treatment of renal cell carcinoma (RCC). However, prognostic factors are still lacking in this context. The aim of this study was to evaluate prognostic factors in RCC patients treated with second- or third-line cabozantinib. A multicenter retrospective real-world study was conducted, involving 32 worldwide centers. A total of 237 patients with histologically confirmed clear-cell and non-clear-cell RCC who received cabozantinib as second- or third-line therapy for metastatic disease were included. We analyzed overall survival (OS), progression-free survival (PFS) and time-to-strategy failure (TTSF) using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses.The median PFS and OS of cabozantinib were 7.76 months (95% CI 6.51-10.88) and 11.57 months (95% CI 10.90-not reached (NR)) as second-line and 11.38 months (95% CI 5.79-NR) and NR (95% CI 11.51-NR) as third-line therapy. The median TTSF and OS were 11.57 and 15.52 months with the sequence of cabozantinib-nivolumab and 25.64 months and NR with nivolumab-cabozantinib, respectively. The difference between these two sequences was statistically significant only in good-risk patients. In the second-line setting, hemoglobin (Hb) levels (HR= 2.39; 95% CI 1.24-4.60, p = 0.009) and IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) group (HR = 1.72, 95% CI 1.04-2.87, p = 0.037) were associated with PFS while ECOG-PS (HR = 2.33; 95%CI, 1.16-4.69, p = 0.018) and Hb levels (HR = 3.12; 95%CI 1.18-8.26, p = 0.023) correlated with OS at multivariate analysis, while in the third-line setting, only Hb levels (HR = 2.72; 95%CI 1.04-7.09, p = 0.042) were associated with OS. Results are limited by the retrospective nature of the study.This real-world study provides evidence on the presence of prognostic factors in RCC patients receiving cabozantinib.

12.
Urology ; 124: 154-159, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30448368

RESUMO

OBJECTIVE: To investigate whether patients requiring dialysis are a higher risk surgical population and would experience more perioperative adverse events even when undergoing a perceived less invasive operation as a laparoscopic radical nephrectomy (LRN). LRN is generally a well-tolerated surgical procedure with minimal morbidity and mortality. Prior to transplantation, dialysis patients will often have to undergo a LRN to remove a native kidney with a suspicious mass. MATERIALS AND METHODS: Patients in the American College of Surgeons National Surgical Quality Improvement Program who underwent a LRN between 2011 and 2016 were included. Patients were stratified by the need for preoperative dialysis 2 weeks prior to surgery, and perioperative outcomes were compared. A multivariable logistic regression analysis was performed to test the association between the need for preoperative dialysis and perioperative risk. RESULTS: There were 8315 patients included in this analysis of which 445 (5.4%) patients required preoperative dialysis. Patients who required preoperative dialysis had more minor (P <.0001) and major (P = .0025) complications, a higher rate of return to the operating room (P = .002), and a longer length of stay (P <.0001) than those patients not requiring preoperative dialysis. In a multivariate analysis, the need for preoperative dialysis was independently associated with adverse perioperative outcomes (OR= 1.45, CI = 1.08-1.95, P = .015). CONCLUSION: Patients requiring preoperative dialysis were more likely to experience a perioperative complication and have a longer length of stay. For LRNs performed prior to transplantation, further risk stratification is needed, and treatment sequencing may need to be reconsidered.


Assuntos
Laparoscopia , Nefrectomia/métodos , Cuidados Pré-Operatórios , Diálise Renal , Adulto , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Melhoria de Qualidade , Medição de Risco , Resultado do Tratamento
13.
14.
Ochsner J ; 17(4): 331-334, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29230117

RESUMO

Background: Late relapse with presentation of metastatic disease >5 years after nephrectomy with curative intent is a known behavior of renal cell carcinoma (RCC), but data on outcomes, especially regarding targeted therapies, are limited. In this study, we analyze clinicopathologic features and response to targeted therapy in patients with late-relapse metastatic RCC (mRCC). Methods: We retrospectively reviewed clinical data on consecutive patients treated with targeted therapy for mRCC diagnosed >5 years after nephrectomy with curative intent. Results: A total of 24 patients (100% clear cell histology, median age 72 years, 83% males, all with prior nephrectomies) met inclusion criteria; 71% had favorable risk, and 25% had intermediate risk by International Metastatic Renal Cell Carcinoma Database Consortium criteria. The estimated median overall survival for all patients was 60.5 months, and the 3-year overall survival rate was 71.78% (95% confidence interval, 47.98%-84.77%). All patients were treated with targeted therapy; first-line treatments included pazopanib (46%), sorafenib (25%), sunitinib (17%), and cytokine (13%), with no significant difference in time to treatment failure between therapies. Median time on first-line therapy was 19.7 months; 67% of patients received second-line treatment. Metastases were detected at considerable rates in sites considered historically uncommon, such as the pancreas, adrenal glands, and soft tissue. Conclusion: Patients with late-relapse mRCC treated with targeted therapy had prolonged survival that compared favorably to historical controls, and metastases in uncommon sites were noted.

15.
AJR Am J Roentgenol ; 209(6): 1278-1284, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29064751

RESUMO

OBJECTIVE: The purpose of this study is to compare the prognostic value of various solid tumor response criteria as well as the additive value of clinical risk factors in patients with advanced renal cell carcinoma (RCC). MATERIALS AND METHODS: Two sets of CT scans (pretreatment scans and scans obtained 1-3.5 months after treatment) were reviewed for 57 patients with metastatic RCC treated with pazopanib in the salvage setting. Tumor response on the posttherapy scan was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) and Choi, modified Choi (mChoi), MASS (Morphology, Attenuation, Size, and Structure), and 10% threshold criteria. In addition, combined Memorial Sloan-Kettering Cancer Center (MSKCC) risk factors plus imaging criteria were used to define response groups. Response evaluations using these criteria were correlated with overall survival (OS) and progression-free survival (PFS), with use of the log-rank test. RESULTS: Patients classified as having progressive disease (PD) on the basis of RECIST, mChoi, and MASS criteria had a significantly worse OS than patients with stable disease (SD) and partial response (PR). With the addition of MSKCC risk factors, all groups with PD defined by combined criteria had significantly worse OS. For 37 patients with no or one MSKCC risk factor, response groups defined by Choi, mChoi, MASS, and 10% threshold criteria did not differ in PFS or OS. However, among 20 patients with two to three MSKCC risk factors, those classified as having PR had longer PFS than did those with SD and had longer OS than did those with PD. CONCLUSION: For patients with advanced RCC for which prior therapies have failed, the prognostic value of various imaging-based tumor response criteria differs on the basis of the MSKCC clinical risk status.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Terapia de Salvação , Sulfonamidas/uso terapêutico , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Carcinoma de Células Renais/patologia , Meios de Contraste , Progressão da Doença , Feminino , Humanos , Indazóis , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Fatores de Risco
16.
Am J Clin Oncol ; 40(2): 189-193, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25222071

RESUMO

BACKGROUND: Ewing sarcoma family of tumors (ESFT) of the kidney are exceedingly rare. Given the rarity of this neoplasm and the complexity associated with its management, information regarding treatment and outcome is warranted. MATERIALS AND METHODS: We conducted a retrospective study of patients with ESFT of the kidney who were treated at MDACC between January 1, 2001 and January 1, 2011. Descriptive statistics were used. RESULTS: Thirteen patients were identified (median age, 33 y; male:female 11:2). Common presenting symptoms were back pain, flank pain, and hematuria. Six patients had metastatic disease at presentation. Initial diagnostic biopsy was performed in 6 patients. Immunohistochemistry showed strong positivity for CD99 (mic2) and cytogenetic analysis demonstrated evidence of EWSR1 fusion gene in 8 cases. Nine patients underwent nephrectomy. Frequently used chemotherapy regimens consisted of vincristine, doxorubicin, and ifosfamide. Median overall survival was 17.2 months. Three patients were alive at the time of analysis, at 2, 7, and 11 years from diagnosis (the latter without evidence of disease). CONCLUSIONS: Renal ESFT carry a guarded prognosis with limited response to therapy and short median overall survival. For patients with metastatic disease, diagnostic biopsy and sarcoma-based chemotherapy regimens are recommended as upfront therapeutic strategy. The role of nephrectomy in the metastatic setting is unclear. Future studies with novel therapies are needed.


Assuntos
Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
17.
Clin Genitourin Cancer ; 15(2): e205-e208, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27568124

RESUMO

BACKGROUND: Pazopanib is associated with increased progression-free survival (PFS) in clear-cell renal cell carcinoma (RCC) and has become a standard of care in this disease. The drug is used in metastatic non-clear-cell RCC, but data on outcomes in this setting are limited. PATIENTS AND METHODS: We conducted a retrospective data analysis of records of consecutive metastatic non-clear-cell RCC patients who received pazopanib in front-line and salvage settings between November 2009 and November 2012. Tumor response rate was assessed by a blinded radiologist using Response Evaluation Criteria in Solid Tumors version 1.1. PFS and overall survival (OS) times were estimated using Kaplan-Meier methods. RESULTS: Twenty-nine patients were identified with non-clear-cell metastatic RCC, 9 received pazopanib in the front-line setting, 20 in the salvage setting after progression of disease with other targeted therapies. Seven patients (24%) had papillary RCC, 4 (14%) had chromophobe, 5 (17%) had unclassified histopathology, and 13 (45%) had other subtypes including collecting duct, translocation Xp11.2, and various subtypes with sarcomatoid differentiation. All patients discontinued pazopanib before analysis. Median PFS was 8.1 months (95% CI, 5.7-NA [not available]) in the front-line group, and 4 months (95% CI, 2.1-9.9) in the salvage group. Median OS was 31 months (95% CI, 9.2-NA) in the front-line group, and 13.6 months (95% CI, 6.4-NA) in the salvage group. CONCLUSION: Pazopanib showed efficacy in patients with metastatic non-clear-cell RCC in the front-line and salvage settings. Toxicity was mild to moderate and manageable. Further studies are needed to evaluate pazopanib's role in non-clear-cell RCC in terms of efficacy and safety.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Indazóis , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Pirimidinas/uso terapêutico , Estudos Retrospectivos , Sulfonamidas/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
18.
Curr Drug Targets ; 17(7): 777-82, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26898309

RESUMO

Innate and adaptive immunity are both involved in prostate cancer (PCa) carcinogenesis and progression. On this scenario, several immunotherapeutic approaches have been proposed and are presently under extensive investigation in PCa patients. Among emerging immune targets, immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), anti-Programmed death-1 (PD-1) and anti-Programmed death-ligand-1 (PD-L1) agents seem to represent the most promising candidate for these patients, together with oncolytic viruses and vaccines, used alone or in combined strategies. In this review, we focused on emerging immunotherapeutic approaches in patients with PCa, showing the rational for their association with current standard therapies including anti-androgen agents, chemo- or radiation therapy.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores , Imunoterapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias da Próstata/tratamento farmacológico , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antígeno B7-H1/metabolismo , Antígeno CTLA-4/metabolismo , Vacinas Anticâncer/uso terapêutico , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Masculino , Terapia de Alvo Molecular/métodos , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias da Próstata/imunologia , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
19.
Curr Drug Targets ; 17(7): 757-70, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26844572

RESUMO

Bladder cancer treatment, namely systemic therapy, was dominated in the last three decades due to the absence of newer therapeutic options other than chemotherapy regimens. Chemotherapy, by itself, both in first and second-line seems to have achieved the modest plateau of its possibilities at the cost of non-negligible toxicity. Targeted therapies, which changed the therapy of many different tumors, seem rather ineffective in bladder cancer. More recently, a new generation of Immunotherapy based regimens represent the most promising avenue for the future systemic treatment of bladder cancer. Checkpoint inhibition, namely PD1/PD-L1 pathway inhibition, showed impressive results in many other tumor types and are expected to become a major player in the treatment of bladder cancer. Other immunotherapy strategies such as fusion proteins represent distant, although promising, options. A brief overview of the current status of bladder cancer immunotherapy is presented.


Assuntos
Antineoplásicos/uso terapêutico , Terapia Genética/métodos , Imunoterapia/métodos , Neoplasias da Bexiga Urinária/terapia , Animais , Antineoplásicos/farmacologia , Antígeno B7-H1/metabolismo , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/imunologia , Vacinação/métodos
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