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1.
Crit Rev Oncol Hematol ; 170: 103579, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35007699

RESUMO

Immune checkpoint inhibitors (ICIs) have led to a significant change in the treatment of urological tumors where several agents are currently approved. Yet, most patients discontinue treatment due to disease progression or after the onset of severe immune-related adverse events (IRAEs). Following promising results in melanoma patients, retreatment with an ICI is receiving increasing attention as an attractive option for selected patients. We performed a literature review focusing on the feasibility, safety, timing and activity of ICI rechallenge in genitourinary cancers where very little information is available. We classified the different ICI retreatment strategies into three main clinical scenarios: retreatment after terminating a prior course of ICI while still on response; retreatment after interruption due to IRAEs; retreatment after progression while on ICI therapy. The pros and cons of these options in the field of urological tumors are then discussed, and critical suggestions proffered for the design of future clinical trials.

2.
Crit Rev Oncol Hematol ; : 103568, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34890801

RESUMO

BACKGROUND: Evidence for the choice of second line, standard vs high dose chemotherapy, (SDCT, HDCT) for patients with relapsed germ cell tumors (GCTs) comes mainly from retrospective studies. MATERIAL AND METHODS: relevant literature was reviewed, considering as endpoints both survival and long term quality of life (QoL). Patients with metastatic GCT progressing after first-line treatment at our Institution were retrospectively evaluated. RESULTS: HDCT seems to achieve a higher rate of long-term remissions. QoL data for this group of patients are lacking. Our experience on 29 patients was in line with these results. Two-year OS for the 18 patients treated with one or two HDCT/PBSCT procedures was 47.5%, while 2-year PFS was 44%. For the 11 receiving SDCT 2-year OS was 36.4%, and 2-year PFS was 32.7%. CONCLUSIONS: HDCT/PBSCT confirmed to be effective in treating patients with relapsed GCT, but prospective studies are needed.

3.
Expert Rev Anticancer Ther ; : 1-7, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34738499

RESUMO

BACKGROUND: Cabozantinib improves survival in metastatic renal cell carcinoma (mRCC) after prior antiangiogenics. The best treatment at disease progression (PD) is unknown. Being also a AXL/MET inhibitor, involved in acquired resistance, we hypothesized a prolonged tumor growth control in patients continuing cabozantinib despite PD. RESEARCH DESIGN AND METHODS: This retrospective multicenter study enrolled patients receiving cabozantinib after the first line between 2014 and 2020. We compared patients maintaining cabozantinib after first PD due to clinical benefit and good tolerability with those who changed therapy. The postprogression survival (PPS) of both was our primary endpoint. RESULTS: We analyzed 89 patients: 45 received cabozantinib beyond PD and 44 switched therapy. 40.4%, 31.5%, and 28.1% of patients received 1, 2, or >2 prior treatment, respectively. 84.3% were intermediate-poor International Metastatic Renal Cell Carcinoma Database risk. Patients continuing cabozantinib showed a higher response rate to cabozantinib before PD (46.7% vs 25%, p = 0.03) and were more heavily pretreated. Continuing cabozantinib showed a significantly longer PPS compared with switching therapy (median PPS 16.9 vs 13.2 months, HR 0.66, 95%CI 0.48-0.92, p = 0.011). CONCLUSIONS: We observed longer PPS in patients continuing cabozantinib beyond PD, suggesting that this could be an effective option.

4.
Oncology ; 99(12): 747-755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34583356

RESUMO

INTRODUCTION: Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, and VEGFR-3, recently approved in Europe for the first-line treatment of metastatic renal cell carcinoma (mRCC). METHODS: Retrospective analysis of safety and activity of tivozanib administered at 1.34 mg daily (3 weeks on, 1 week off) within a compassionate-use program to patients with mRCC with no prior systemic treatment in Italy. RESULTS: From August 2018 to April 2019, 64 patients have started tivozanib in 9 oncology units. The median age was 67.5 years (range 40-85), 62.5% males. According to International Metastatic Renal Cell Carcinoma Database Consortium criteria, 27.1% of patients were good prognosis, 57.6% intermediate, and 15.3% poor. Primary tumor had been removed in 71.9% of patients. Histology was clear cell 89%, papillary 4.7%, and unclassified 6.3%. The response rate was 34.4%, stable disease 40.6%, and progression 15.6%. Grade 3-4 toxicities were 7.8% hypertension, 4.7% anemia, 3.1% mucositis, 3.1% asthenia, 1.6% diarrhea, 1.6% anorexia, 1.6% worsening of renal function, and 3.1% cardiac events. Dose reduction to 0.89 mg was applied to 17.2% of patients, and the discontinuation rate due to toxicity was 5.8%. Median progression-free survival was 12.4 months, with 68.7% of patients alive at 12 months. The developing of hypertension predicted increased progression-free survival at multivariate analysis (HR, 0.128; 95% CI, 0.03-0.59; p = 0.008). CONCLUSIONS: Tivozanib showed good activity and favorable safety profile in a real-world cohort of unselected patients with mRCC. Predictive biomarkers of response to antiangiogenic therapy are urgently needed in order to identify RCC patients who could still receive a monotherapy with VEGFR inhibitors in the first line.

5.
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
6.
Am J Clin Oncol ; 44(3): 121-125, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33617179

RESUMO

OBJECTIVES: The aim of our study was to collect data about of the outcome of metastatic renal cell carcinoma patients who progressed after immune checkpoint inhibitors in order to enhance data about efficacy and safety of treatment beyond immune-oncology (IO). MATERIALS AND METHODS: A total of 162 eligible patients, progressing to IO, were enrolled from 16 Italian referral centers adhering to the Meet-Uro association. Baseline characteristics, outcome data and toxicities were retrospectively collected. Descriptive analysis was made using median values and ranges. Kaplan-Meier method and Mantel-Haenszel log-rank test were performed to compare differences between groups. RESULTS: A total of 111 patients (68.5%) were treated after IO progression. In all, 51 patients (31.5%) did not receive further treatment for clinical deterioration. Median IO progression free survival (PFS) was 4 months (95% confidence interval [CI]: 3.1-4.8). IO-PFS tends to be longer in patients reporting adverse events (AE) of any grade (5.03 [95% CI: 3.8-6.1] vs. 2.99 [95% CI: 2.4-3.5] months P=0.004). Subsequent therapies included cabozantinib (n=79, 48%), everolimus (n=11, 6.7%), and others (n=21, 12.9%).Median PFS post-IO was 6.5 months (95% CI: 5.1-7.8). Cabozantinib showed longer PFS compared with everolimus (7.6 mo [95% CI: 5.2-10.1] vs. 3.2 mo [95% CI: 1.8-4.5]) (hazard ratio: 0.2; 95% CI: 0.1026-0.7968) and other drugs (4.3 mo [95% CI: 1.3-7.4]) (hazard ratio: 0.6; 95% CI: 0.35-1.23). All grade AE were reported in 83 patients (74%) and G3 to G4 AE in 39 patients (35%). Target therapies post-IO showed median overall survival of 14.7 months (95% CI: 0.3-21.4). CONCLUSIONS: In our real world experience after progression to IO, vascular endotelial groth factor-tyrosine kinase inhibitors, given to patients, proved to be active and safe choices. Cabozantinib was associated with a better outcome in terms of median PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Idoso , Anilidas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Progressão da Doença , Everolimo/administração & dosagem , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Itália , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/metabolismo , Piridinas/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento
7.
Anticancer Drugs ; 32(2): 222-225, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32868643

RESUMO

In the past few years, the immune checkpoint inhibitor (ICI) nivolumab has become standard of care in the treatment of metastatic renal cell carcinoma (mRCC) progressing after antiangiogenic agents. To date, neither expression of programmed death ligand-1 (PD-L1) nor any other biomarker can be used to predict responses to ICIs, although intermediate-poor International Metastatic Database of Renal Carcinoma (IMDC) risk patients and those with sarcomatoid tumors appear to achieve superior benefit from immunotherapy. Paradoxically, ICIs may sometimes increase the speed of tumor growth. This rare phenomenon, called hyperprogression, has first been described in patients with melanoma and lung cancer treated with ICIs and is associated with poor survival. Here, we present the case of a patient affected by an intermediate IMDC risk mRCC with diffuse sarcomatoid features who achieved long disease control with first-line sunitinib and then started a second-line treatment with nivolumab. Unexpectedly, he experienced a dramatic acceleration of tumor growth and died soon after the third infusion of nivolumab. Then, we review the frequency of hyperprogression in mRCC and discuss the biological peculiarity of sarcomatoid RCC in terms of different responses to ICIs and antiangiogenic agents.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Nivolumabe/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Nivolumabe/uso terapêutico
8.
J Geriatr Oncol ; 12(2): 290-297, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32972885

RESUMO

BACKGROUND: There is poor data on the prognostic role of Comprehensive Geriatric Assessment (CGA) in older patients with metastatic renal cell carcinoma (mRCC) treated with first line Tyrosine Kinase Inhibitors (TKIs). MATERIALS AND METHODS: We retrospectively reviewed the clinical charts of mRCC patients older than 70 years treated at our Institute with first-line Sunitinib or Pazopanib for at least 6 months. Every patient received a CGA at baseline and was identified as fit, vulnerable or frail according to Balducci's Criteria. We then assessed the impact of CGA category on survival, disease control and tolerability of TKIs. RESULTS: We identified 86 eligible patients. Median age: 74.5 years, 56% males; 45.4% were fit, 37.2% vulnerable and 17.4% frail at CGA. There were no significant differences in the rate of Grade (G)1-2 and G3-4 toxicities, dose reduction rates, PFS and OS between Sunitinib and Pazopanib. Fit, vulnerable and frail patients achieved significantly different median PFS (18.9 vs 11.2 vs 5.1 months; p < 0.001) and OS (35.5 vs 14.6 vs 10.9 months; p < 0.001). Patients categorized as fit had higher chance of receiving a second-line treatment (66.6% vs 28.9% in vulnerable/frail; p = 0.002). The incidence of G3/4 events was significantly lower in the fit subgroup (19% vs 45% in vulnerable/frail; p = 0.0025). CONCLUSIONS: In our retrospective single-center experience, CGA could accurately discriminate patients with higher risk of experiencing G3/4 toxicities, shorter PFS, and lower chance of receiving a second line treatment. CGA strongly impacted on OS, independently from International mRCC Database Consortium (IMDC) classification.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Idoso , Carcinoma de Células Renais/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Avaliação Geriátrica , Humanos , Indazóis , Neoplasias Renais/tratamento farmacológico , Masculino , Prognóstico , Pirimidinas , Estudos Retrospectivos , Sulfonamidas , Sunitinibe/uso terapêutico , Resultado do Tratamento
9.
Prostate Cancer Prostatic Dis ; 23(4): 654-660, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32651468

RESUMO

BACKGROUND: Cancer-related pain, usually associated with bone metastases, is a frequent and debilitating morbidity in patients with prostate cancer. To date there are only limited data regarding the prognostic role of pain in men with metastatic castration-sensitive prostate cancer (mCSPC). The objective of our analysis was to assess if the presence of pain can be considered an independent prognostic factor in mCSPC patients. METHODS: A retrospective analysis was performed on patients with mCSPC referring to six oncology centers in Italy. Clinical and pathological features were recorded. Patients were considered to have pain if this was reported within the patient's file or in case of a chronic analgesic therapy was found among the concomitant medications. Survivals were estimated by the Kaplan-Meier method, and compared across groups using the log-rank test. Cox proportional hazard models, stratified according to the baseline characteristics, were used to estimate hazard ratios for overall survival (OS). All the variables were significant if p < 0.05. RESULTS: Data about pain were available for 365 cases and pain was present in 34.8% of patients. Pain was mainly associated with high value of prostate-specific antigen, metastatic bone extension regardless of the site, and lymph node involvement. mCSPC patients with pain had in most of the cases high-volume or Hr disease, and significant shorter OS (27.0 vs. 58.2 months, p < 0.001) and PFS (10.1 vs. 17.4 months, p < 0.001) compared to those without pain. The negative impact of pain on OS remained significant even if adjusted for CHAARTED or LATITUDE classification, and other significant baseline prognostic factors. CONCLUSIONS: This analysis supports the poor prognostic role of cancer-related pain in the setting of mCSPC patients. A prospective validation is required.


Assuntos
Dor do Câncer/epidemiologia , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Idoso , Antagonistas de Androgênios/uso terapêutico , Neoplasias Ósseas/sangue , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/secundário , Dor do Câncer/diagnóstico , Dor do Câncer/mortalidade , Dor do Câncer/patologia , Ensaios Clínicos como Assunto , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Taxa de Sobrevida
10.
Support Care Cancer ; 28(10): 4687-4695, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31960124

RESUMO

PURPOSE: To evaluate adherence to abiraterone or enzalutamide for the treatment of metastatic castration-resistant prostate cancer (mCRPC). METHODS: In an observational prospective cohort study, we monitored patients with mCRPC for their adherence to abiraterone or enzalutamide in the pre- or post-chemotherapy setting. RESULTS: Fifty-eight patients with median age of 76 years (range 56-94), age-adjusted Charlson comorbidity score of 10 (range, 4-15), and geriatric G8 score of 14 (range, 6-17) were enrolled. Twenty-two (38%) patients were treated with abiraterone and 36 (62%) with enzalutamide, while forty-two (72%) were in the pre-chemotherapy setting. Forty-seven patients (81%) had a caregiver. Based on the pill counting, a non-adherence rate of 4.8% and 6.2% was observed for the whole period and the first 3 months, respectively, without a statistically significant difference between abiraterone and enzalutamide cohorts. A lower non-adherence rate (1.3%) was reported by patients during the whole period, mainly due to a misperception (77%) and forgetfulness (19%). Non-adherence rate to the fulfilling of the clinical diary was 38% for the whole period. Non-adherence in the whole period was related to the radiological response (p = 0.03) and geriatric G8 score (p = 0.005). By the receiver operating characteristic (ROC) curve based on the radiological response, non-adherence cut-off was 1.87% (p = 0.04). By this non-adherence cut-off, the G8 cut-off was 14.75 (p = 0.0003). CONCLUSION: Non-adherence to abiraterone or enzalutamide for mCRPC may have an impact on disease response and be related to patients' frailty, suggesting their geriatric assessment and clinical interventions to monitor and increase their adherence.


Assuntos
Androstenos/administração & dosagem , Adesão à Medicação , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Nitrilas , Feniltioidantoína/administração & dosagem , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/patologia , Resultado do Tratamento
11.
J Immunother ; 42(7): 269-273, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31261165

RESUMO

De novo metastatic castration-sensitive prostate cancer (mCSPC) is small subgroup of prostate cancer associated with poor prognosis. The aim of our study was to assess the expression of programmed death-ligand 1 (PD-L1) in tumor cells of de novo mCSPC patients. Patients referred to our institution from January 2007 to October 2017 with de novo mCSPC and available diagnostic tissue were included. We tested the PD-L1 pharmaDx qualitative immunohistochemical assay, a monoclonal rabbit anti-PD-L1, clone 28-8 intended for use in the detection of PD-L1 protein in formalin-fixed paraffin-embedded. Kaplan-Meier method was used to estimate survivals according to the expression of PD-L1. The study population included 32 de novo mCSPC patients, analyzed for PD-L1 expression using 2 cut-off values (1% and 5%) to define the positivity. Total of 46.9% of cases had tumor PD-L1 expression ≥1%, and 31.3% had expression ≥5%. No differences were found between the PD-L1 expression ≥1% and the involvement of liver, lung, and number of bone metastases, and the disease volume based on CHAARTED classification. PD-L1 tumors had higher incidence of Gleason score ≥8 compared with PD-L1 tumors (P=0.037), while the incidence of lymph node metastases was higher in PD-L1 tumors (P=0.044). No difference in the median overall survival (mOS) was observed between the PD-L1 population and the PD-L1 patients (43.8 vs. 29.6 mo; P=0.88). The tumor PD-L1 expression cannot be considered a prognostic factor for de novo mCSPC, even if its prognostic and predictive significance have to be thoroughly investigated to better define the selected group of prostate cancer patients that might benefit from checkpoint blockade immunotherapy.


Assuntos
Antígeno B7-H1/genética , Biomarcadores Tumorais , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/metabolismo , Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/mortalidade , Resultado do Tratamento
12.
Br J Clin Pharmacol ; 85(6): 1283-1289, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30740760

RESUMO

AIMS: Data regarding the cardiac toxicity of cabozantinib lacks. The aim of our study was to assess the risk of cabozantinib-related cardiotoxicity in mRCC patients. METHODS: We performed a multicentre prospective study on mRCC patients treated with cabozantinib between October 2016 and November 2017. Transthoracic echocardiogram and plasma biomarkers assay were assessed at baseline, 3 and 6 months after cabozantinib initiation. RESULTS: The study population included 22 mRCC patients. At baseline, 9.1% had a reduced left ventricular ejection fraction (LVEF), but none had a left ventricular systolic dysfunction. Patients with baseline reduced LVEF did not show further significant LVEF modification after 3 months. After 6 months, only 1 had an LVEF decline >10% compared to baseline, resulting in LV systolic dysfunction. At baseline, 64.7% and 27.3% of patients had elevated precursor brain natriuretic peptide (proBNP) and high-sensitivity troponin I (hsTnI), respectively. Among patients with basal normal proBNP and hsTnI, none had elevated values at 3 and 6 months. No correlation was found between basal elevated proBNP and basal reduced LVEF (P = .29), and between elevated proBNP and reduced LVEF after 6 months (P = .37). Similarly, we found no correlations between elevated hsTnI and reduced LVEF or elevated proBNP at baseline (P = .47; P = .38), at 3 (P = .059; P = .45) and after 6 months (P = .72; P = 1.0). CONCLUSIONS: This prospective study revealed a modest risk of developing left ventricular systolic dysfunction related to cabozantinib. A lack of correlation between elevated cardiac biomarkers and reduced LVEF at different time-points was detected. Assessments of the cardiac function should be reserved at the occurrence of clinical symptoms.


Assuntos
Anilidas/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Piridinas/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente , Idoso , Biomarcadores/sangue , Carcinoma de Células Renais/secundário , Cardiotoxicidade , Feminino , Humanos , Incidência , Itália/epidemiologia , Neoplasias Renais/patologia , Masculino , Peptídeo Natriurético Encefálico/sangue , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Troponina I/sangue , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular/efeitos dos fármacos
13.
Semin Oncol ; 46(1): 65-72, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30665685

RESUMO

There is no second-line standard of care universally accepted for platinum-refractory metastatic urothelial carcinoma. Immunotherapy and anti-VEGF(R) targeted therapies are 2 emerging strategies with promising though inconclusive results. We perform a systematic meta-analysis to assess the available options. We searched MEDLINE/PubMed, the Cochrane Library, and American society of clinical oncology (ASCO) Meeting abstracts to identify prospective studies. Data extraction was conduced according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The measured outcomes were overall survival (OS) and progression free survival (PFS). Seven randomized controlled trials were selected for final analysis, with a total of 2,451 evaluable patients. Chemotherapy with vinflunine did not reduce the risk of progression (HR = 1.11; 95%CI 0.78-1.57; P = .56) or death (HR = 0.97; 95%CI 0.70-1.34; P = .87) compared to taxanes. Immunotherapy with anti-PD-1/PD-L1 mAb improved OS over chemotherapy (HR = 0.81; 95% CI 0.71-0.92; P<.0009). The OS benefit of immunotherapy was retained when compared to taxanes, but not compared to vinflunine, although without a significant difference between the 2 subgroups (P = .30). A lack of PFS (HR = 0.73; P = .08) and OS (HR = 1.0; P = .99) benefit was observed with an anti-VEGF(R) plus chemotherapy compared to chemotherapy alone. No PFS (P = .14) or OS (P = .13) differences were detected when comparing anti-VEGF(R) ± chemotherapy and immunotherapy. Immunotherapy significantly improved OS compared to chemotherapy in metastatic urothelial carcinoma unselected for PD-L1 status. The addition of anti-VEGF(R) to chemotherapy did not provide any statistically significant benefit in terms of PFS or OS. Single agent taxanes or vinflunine can be considered given their similar efficacy but different toxicity profiles.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma/tratamento farmacológico , Urotélio/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma/imunologia , Carcinoma/patologia , Intervalo Livre de Doença , Tratamento Farmacológico/tendências , Humanos , Imunoterapia/tendências , Estadiamento de Neoplasias , Resultado do Tratamento , Urotélio/patologia
14.
Urol Oncol ; 36(12): 526.e13-526.e18, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30301699

RESUMO

BACKGROUND: Despite important results achieved for metastatic renal cell carcinoma, some patients could benefit from local treatments or an initial active surveillance (AS) period for recurrent disease. We aim to analyze: changes in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk class, the number of metastases and the disease burden from the start of AS to the beginning of systemic therapy; and if these changes influenced patient outcomes. PATIENTS AND METHODS: Patients who started AS at our institution from January 2007 to April 2016 were included. The Kaplan-Meier method was used to estimate total overall survival (tOS) and progression-free survival. Changes in IMDC class, number of metastatic sites, and tumor burden (TB) were evaluated and related to patient survival. Among the patients who started active treatment, progression-free survival and post surveillance OS (psOS) were evaluated. RESULTS: 52 patients were included in the analysis. Median time on AS and tOS were 18.3 and 80.1 months respectively. Baseline factors were not related to the time on AS apart from the IMDC classification (HR = 2.15; 95% CI: 1.19-3.87; P = 0.011). The increase in the number of metastatic sites during AS was correlated with poor tOS (HR = 2.86; 95% CI: 1.29-6.34; P = 0.010). The increase of the TB was a negative prognosis factor for tOS (HR = 1.16; 95% CI: 1.02-1.31; P = 0.024) and psOS (HR = 1.21; 95% CI: 1.07-1.40; P = 0.004). Both IMDC class and change in the TB at the start of therapy were related to psOS. The retrospective nature and the lack of an external review of the imaging are its main limitations. CONCLUSIONS: During AS, patients rarely experience a deterioration of their IMDC prognostic class, and the change in the TB, more than the increase in the number of metastatic sites, may help physicians to make decisions about the early termination of AS and the start of systemic therapy.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/secundário , Vigilância da População , Carga Tumoral , Idoso , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Renais/classificação , Neoplasias Renais/cirurgia , Metástase Linfática , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Taxa de Sobrevida
15.
Target Oncol ; 13(5): 649-655, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30167971

RESUMO

BACKGROUND: The CHAARTED and LATITUDE trials demonstrated improved outcomes with docetaxel or abiraterone plus androgen deprivation therapy in metastatic hormone sensitive prostate cancer (mHSPC) using two different prognostic scores. OBJECTIVE: The aim of our study was to assess the concordance between the two scores and if these retained their prognostic value exclusively in de novo mHSPC. PATIENTS AND METHODS: De novo mHSPC patients referring to our institution were retrospectively stratified according to the CHAARTED and LATITUDE classifications: high volume/high risk (HV/HR), low-volume/low-risk (LV/LR), and HVorHR (HV/LR and LV/HR). The Kaplan-Meier method and Cox proportional-hazard models were used to estimate hazard ratios for overall survival. RESULTS: The study population included 106 patients. Concordance between the CHAARTED and LATITUDE classifications was observed in 86.8% of cases (65.1% HV/HR, 21.7% LV/LR), while 13.2% of patients fulfill the criteria of only one of the two classifications (HVorHR). When analyzed independently, the CHAARTED and LATITUDE classifications maintained their prognostic value (mOS 28.2 months in HV versus 60.9 months in LV, p = 0.006; 28.2 months in HR versus 40.6 months in LR, p = 0.017). The LR/LV population showed significantly longer mOS compared to the HR/HV group (72.6 months versus 26.3 months; p = 0.005), and to HVorHR patients (35.1 months; p = 0.003). No difference in OS was observed between HV/HR and HVorHR patients. ECOG PS ≥ 1 and patient age improved the prognostic value of the two classifications with multivariate analysis. CONCLUSIONS: Our study showed a lack of complete concordance between the CHAARTED and LATITUDE classifications. The analysis confirmed the role of these prognostic scores to stratify de novo mHSPC patients in clinical practice.


Assuntos
Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Humanos , Masculino , Metástase Neoplásica , Prognóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia
16.
Cancer Treat Rev ; 70: 67-74, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30121492

RESUMO

De novo metastatic castration sensitive prostate cancer (mCSPC) accounts for about 4% of all prostate tumors in Western Countries. This condition has a heterogeneous biological e clinical behavior, ranging from indolent to aggressive and rapidly fatal forms. Recently, the therapeutic landscape for mCSPC has been broadly enriched; indeed robust evidence supports the addiction of chemotherapy (docetaxel) or abiraterone acetate to androgen deprivation therapy (ADT), the latter considered for long the unique standard of care. However, the prognostic stratification and the definition of the ideal therapeutic approach for the subpopulation of de novo mCSPC - albeit largely represented in pivotal clinical trials enrolling mCSPC patients - have yet to be prospectively outlined. The aim of this review was to describe the current state of art about clinical presentation, prognostic classification, and different therapeutic options available for de novo mCSPC patients. Furthermore, we shed light on ongoing clinical trials and future perspectives for this disease setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/secundário , Progressão da Doença , Humanos , Masculino , Prognóstico
17.
Cancer Treat Rev ; 70: 112-117, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30145397

RESUMO

BACKGROUND: Recently, immune checkpoint inhibitors against PD-1/PD-L1 or CTLA4 have emerged as new treatments for metastatic renal cell carcinoma (mRCC), despite discrepancy between their effects on OS and PFS. We performed a meta-analysis of randomized trials comparing immunotherapy to standard of care (SOC) in mRCC. METHODS: Searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts prospective studies were identified. Data extraction was conducted according to the PRISMA statement. The measured outcomes were OS, PFS, and ORR. RESULTS: A total of 2832 patients were available for evaluation of OS, and 3033 for PFS and ORR. Compared to SOC, immunotherapy improved OS (HR = 0.75; 95%CI 0.66-0.85; p < 0.001), and PFS (HR = 0.88; 95%CI 0.80-0.97; p = 0.009). The PFS benefit was not confirmed when considering patients treated in first-line only (p = 0.10). Conversely, significant ORR improvement was found in patients treated in first-line only (HR = 1.14; 95%CI 1.02-1.28; p = 0.03) but not in the overall population. CONCLUSIONS: Immunotherapy improved OS compared to SOC in mRCC, irrespective of treatment line. In first-line, immunotherapy also increased the ORR compared to sunitinib. A lack of correlation between OS and PFS was confirmed, the latter to be used cautiously for the design and interpretation of trials involving immunotherapy in mRCC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Padrão de Cuidado , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/secundário , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/secundário , Prognóstico
18.
Cancer Treat Rev ; 67: 29-33, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29753244

RESUMO

Very interesting issues regarding RCC treatment have been raised during 2017. We analysed the main news that may potentially modified clinical practice. Conflicting data came from trials testing targeted therapies in the adjuvant setting, supporting the necessity of further investigations. One of the key goals of RCC research is focused on the first-line therapy, with particular interest focus on immunotherapy combinations. Redefine the standard of care with the aim of improving patients' survival represents an imperative need. Enhancing immunotherapy antitumor activity by combining immune checkpoint inhibitors with anti-angiogenetic therapies is a noteworthy research field, with promising results. In addiction, we analysed in the metastatic setting data about the role of cytoreductive nephrectomy and the possibility of delay the start of first-line therapy after an active surveillance period. Based on recent developments, the paper outlines future prospective of RCC research.


Assuntos
Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Procedimentos Cirúrgicos de Citorredução , Humanos , Imunoterapia , Nefrectomia , Padrão de Cuidado
19.
Clin Genitourin Cancer ; 16(3): e645-e653, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29339044

RESUMO

INTRODUCTION: The cardiovascular toxicity related to abiraterone and enzalutamide has been previously studied by our group. In this analysis, we aim to update our previous findings related to abiraterone and enzalutamide, including the new available evidence, both in castration-resistant and hormone-sensitive prostate cancer. PATIENTS AND METHODS: Prospective studies were identified by searching the MEDLINE/PubMed, Cochrane Library, and ASCO Meeting abstracts. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods. RESULTS: We included 7 articles in this meta-analysis, covering a total of 8660 patients who were used to evaluate cardiovascular toxicity. The use of new hormonal agents was associated with an increased risk of all-grade (RR, 1.36; 95% CI, 1.13-1.64; P = .001) and high-grade (RR, 1.84; 95% CI, 1.21-2.80; P = .004) cardiac toxicity. The use of new hormonal agents was also associated with an increased risk of all-grade (RR, 1.98; 95% CI, 1.62-2.43; P = .001) and high-grade (RR, 2.26; 95% CI, 1.84-2.77; P = .004) hypertension compared with the controls. Abiraterone was found to significantly increase the risk of both cardiac toxicity and hypertension, whereas enzalutamide significantly increases only the risk of hypertension. No differences were found based on the dose of prednisone used with abiraterone. The major limitation of this study is that data are available only as aggregate, and no single-patient information could be analyzed. CONCLUSIONS: Abiraterone and enzalutamide significantly increase the incidence and RR of cardiovascular toxicity in patients affected by metastatic prostate cancer. Follow-up for the onset of treatment-related cardiovascular events should therefore be considered in these patients.


Assuntos
Androstenos/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Feniltioidantoína/análogos & derivados , Neoplasias da Próstata/tratamento farmacológico , Benzamidas , Doenças Cardiovasculares/induzido quimicamente , Intervalo Livre de Doença , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Incidência , Masculino , Nitrilas , Feniltioidantoína/efeitos adversos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Eur J Cancer ; 83: 237-246, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28756136

RESUMO

AIM: Non-clear cell renal cell carcinoma (nccRCC) tumours include a heterogeneous group of malignancies that profoundly differ in terms of morphology, genetic profile, clinical behaviour and prognosis. The optimal treatment algorithm for nccRCC is still unknown and derived mainly from evidence available for ccRCC, being therefore represented by targeted agents against vascular endothelial growth factor and mammalian target of rapamycin (mTOR) pathways. We aimed to compare the efficacy of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKis) and mTOR inhibitors (mTORi) for the treatment of nccRCC patients. METHODS: Searching the MEDLINE/PubMed, Cochrane Library and American Society of Clinical Oncology Meeting abstracts prospective studies were identified. Data extraction was conduced according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The measured outcomes were progression-free survival (PFS), overall survival (OS) and the overall response rate (ORR). RESULTS: Four randomised controlled trials were selected for final analysis, with a total of 332 patients evaluable for PFS. Treatment with TKi significantly reduced the risk of progression compared with mTORi (hazard ratio [HR] = 0.71; 95% confidence interval [CI] 0.60-0.84; p < 0.0001). This difference remained significant when sunitinib was compared with everolimus in first-line setting (HR = 0.67; 95% CI, 0.56-0.80; p < 0.00001). In the 332 patients evaluable for OS, no significant difference was found between TKi and mTORi (HR = 0.86; 95% CI, 0.67-1.12; p = 0.27). In the 176 evaluable patients, TKis therapy did not improve the ORR when compared with mTORi (relative risk [RR] = 2.21; 95% CI, 0.87-5.60; p = 0.09), even if treatment with sunitinib doubled the probability of achieving a tumour response. CONCLUSIONS: Treatment with TKis significantly improves PFS, but not OS, when compared with mTORi. Moreover, sunitinib as first-line therapy reduces the risk of progression compared with everolimus; therefore, supporting the standard treatment paradigm broadly used for ccRCC patients. The relatively modest efficacy of available targeted therapies reinforces the need of future histology based, molecular driven therapeutic paradigm.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Humanos , Estudos Prospectivos , Proteínas Tirosina Quinases/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
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