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1.
Biologics ; 15: 441-450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754178

RESUMO

In recent years, diagnostic and therapeutic advances have contributed to a reduction in mortality rates of patients with metastatic urothelial carcinoma (mUC). Immune checkpoint inhibitors have demonstrated efficacy and safety as both first-line and first-line switch maintenance therapy for mUC. For platinum-refractory patients, in addition to immunotherapy, other targeted agents (antibody-drug conjugates and fibroblast growth factor receptor inhibitors) have been approved after demonstrating a clinically relevant advantage in overall response rate, progression-free survival, and overall survival compared to standard of care. Sequential treatment strategies are finally feasible for patients with advanced urothelial carcinoma. This review will summarize the results of the most important phase II-III clinical trials for first-line, switch maintenance, second-line, and subsequent lines of therapy, and describe the most promising clinical trials currently ongoing in these treatment scenarios.

2.
Cancer Manag Res ; 13: 7623-7636, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675658

RESUMO

In the last decade, the inhibition of the mechanistic target of Rapamycin (mTOR) in renal clear cell carcinoma (RCC) has disappointed the clinician's expectations. Many clinical trials highlighted the low efficacy and unmanageable safety profile of first-generation mTOR inhibitors (Rapalogs), thus limiting their use in the clinical practice only to those patients who already failed several therapy lines. In this review, we analyze the major resistance mechanisms that undermine the efficacy of this class of drugs. Moreover, we describe some of the possible strategies to overcome the mechanisms of resistance and their clinical experimentation, with particular focus on novel mTOR inhibitors and the combinations of mTOR inhibitors and other anti-cancer drugs.

3.
Ther Adv Urol ; 13: 17562872211054302, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707691

RESUMO

Background: Considering the growing genitourinary (GU) cancer population undergoing systemic treatment with immune checkpoint inhibitors (ICIs) in the context of the COVID-19 pandemic, we planned a clinical audit in 24 Italian institutions treating GU malignancies. Objective: The primary objective was investigating the clinical impact of COVID-19 in GU cancer patients undergoing ICI-based therapy during the first outbreak of SARS-CoV-2 contagion in Italy. Design setting and participants: The included centers were 24 Oncology Departments. Two online forms were completed by the responsible Oncology Consultants, respectively, for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC) patients receiving at least one administration of ICIs between 31 January 2020 and 30 June 2020. Results and limitation: In total, 287 mRCC patients and 130 mUC patients were included. The COVID-19 incidence was, respectively, 3.5%, with mortality 1%, in mRCC patients and 7.7%, with mortality 3.1%, in mUC patients. In both groups, 40% of patients developing COVID-19 permanently discontinued anticancer treatment. The pre-test SARS-CoV-2 probability in the subgroup of patients who underwent nasal/pharyngeal swab ranged from 14% in mRCC to 26% in mUC. The main limitation of the work was its nature of audit: data were not recorded at the single-patient level. Conclusion: GU cancer patients undergoing active treatment with ICIs have meaningful risk factors for developing severe events from COVID-19 and permanent discontinuation of therapy after the infection. Treatment delays due to organizational issues during the pandemic were unlikely to affect the treatment outcome in this population.

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.
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.

6.
Microvasc Res ; 138: 104189, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34062191

RESUMO

Tumor-associated vessels constitution is the result of angiogenesis, the hallmark of cancer essential for tumor to develop in dimension and to spread throughout the organism. Tumor endothelium is configured as an active functioning organ capable of determine interaction with the immune response and all the other components of the variegate cancer microenvironment, determining reciprocal influence. Angiogenesis is here analyzed in its molecular and cellular mechanisms, multiple mediators and principal players, represented by Endothelial Cells. It is discussed the striking heterogeneity of cancer endothelium, due to morphological and molecular aberrations that it often presents and its multiple origin. Among the cells that participate to the composition of tumor vasculature, Endothelial Progenitor Cells represent an important source for physical sustain and paracrine signaling in the process of angiogenesis. Treatment options are reviewed, with particular focus on novel therapeutic strategies for overcoming tumor resistance to anti-angiogenic agents.

7.
J Immunother Cancer ; 9(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34016723

RESUMO

BACKGROUND: Until now, no robust data supported the efficacy, safety and recommendation for influenza vaccination in patients with cancer receiving immune checkpoint inhibitors (ICIs). METHODS: The prospective multicenter observational INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors (INVIDIa-2) study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving ICIs, enrolled in 82 Italian centers from October 2019 to January 2020. The primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020. Secondary endpoints regarded ILI severity and vaccine safety. RESULTS: The study enrolled 1279 patients; 1188 patients were evaluable for the primary endpoint analysis. Of them, 48.9% (581) received influenza vaccination. The overall ILI incidence was 8.2% (98 patients). Vaccinated patients were significantly more frequently elderly (p<0.0001), males (p=0.004), with poor European Cooperative Oncology Group performance status (p=0.009), affected by lung cancer (p=0.01), and by other non-cancer comorbidities (p<0.0001) when compared with unvaccinated. ILI incidence was not different basing on influenza vaccination: the time-to-ILI was similar in vaccinated and unvaccinated patients (p=0.62). ILI complications were significantly less frequent for patients receiving the vaccination (11.8% vs 38.3% in unvaccinated, p=0.002). ILI-related intravenous therapies were significantly less frequent in vaccinated patients than in unvaccinated (11.8% vs 29.8%, p=0.027). ILI lethality was, respectively, 0% in vaccinated and 4.3% in unvaccinated patients. Vaccine-related adverse events were rare and mild (1.5%, grades 1-2). CONCLUSION: The INVIDIa-2 study results support a positive recommendation for influenza vaccination in patients with advanced cancer receiving immunotherapy.

8.
Curr Opin Urol ; 31(3): 236-241, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33742982

RESUMO

PURPOSE OF REVIEW: The treatment landscape of metastatic renal cell carcinoma has greatly evolved over the past fifteen years, leading to a significant improvement in the outcome of our patients. However, there is still an urgent need for predictive biomarkers that could guide our treatment selection, especially in the present era of immune-based treatments. RECENT FINDINGS: A number of putative biomarkers of immunotherapy activity have been proposed over the past few years, including PD-L1 immunohistochemical expression, tumor mutational burden, neoantigens load, insertions and deletions, complex gene signatures, as well as lymphocytic subpopulations (either circulating or tumor-infiltrating). However, despite preliminary intriguing findings, no biomarker for immune checkpoint activity has emerged so far, that could be used in everyday clinical practice, mainly due to preliminary, or frankly, conflicting results. SUMMARY: The quest for an 'ideal' biomarker, which should be characterized by adequate specificity, sensibility, predictive (and not just prognostic) value, robustness, reproducibility, ease of evaluation and low cost, is still ongoing.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Reprodutibilidade dos Testes
9.
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.

10.
Crit Rev Oncol Hematol ; 159: 103235, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33493633

RESUMO

AIM: To compare trimodality therapy (TMT) versus radical cystectomy (RC) and develop GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Recommendation by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) for treatment of muscle-invasive bladder cancer (MIBC). MATERIAL AND METHODS: Prospective and retrospective studies comparing TMT and RC for MIBC patients were included. Qualitative and quantitative evaluation of evidence was made. RESULTS: Ten studies were included in the analysis. Pooled analysis showed salvage cystectomy and pathological complete response rates after TMT of 12 % and 72-77.5 %, respectively. Pooled rates of G3-G4 GU toxicity and serious toxicity rate were 18 vs 3% and 45 vs 29 % for patients undergoing TMT vs RC, respectively. The panel assessed a substantial equivalence in terms of OS and CSS at 5 years between TMT and RC. CONCLUSIONS: TMT could be suggested as an alternative treatment to RC in non-metastatic MIBC patients, deemed fit for surgery.


Assuntos
Cistectomia , Neoplasias da Bexiga Urinária , Humanos , Itália/epidemiologia , Oncologia , Músculos , Invasividade Neoplásica , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/terapia
11.
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
12.
Expert Rev Anticancer Ther ; 21(4): 401-412, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33287612

RESUMO

Introduction: In recent years, the systemic treatment of patients with metastatic renal-cell carcinoma (mRCC) has undergone profound innovations, offering the availability of new drugs, and raising the bar of the survival expectation in this, previously, almost-always, incurable disease. The likeliness of reaching durable response and long-term survival is still closely linked to good clinical management and smart treatment sequencing, rather than to a single systemic treatment choice.Areas covered: We review all systemic therapeutic options currently available, describe the evidence behind the current options available for mRCC patient treatment, and provide our personal cues to support clinical decisions.Expert opinion: The IMDC classification is still the only widely validated tool for the choice of primary therapy. Other elements should then be considered for selecting patients who can still receive TKI monotherapy (good-risk patients) or who deserve an 'all-at-once' approach with TKI plus ICI (poor-risk patients with the high metastatic burden and poor-prognosis organ involvement, likely not able to achieve a second chance), identifying these two 'extreme' situations and setting all the other treatment choices on the basis of several nuances. In the second- and further-line settings, ad-hoc prospective trials are awaited.

13.
Cancer Immunol Immunother ; 70(6): 1667-1678, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33315149

RESUMO

BACKGROUND: It is still unclear how to combine biomarkers to identify patients who will truly benefit from anti-PD-1 agents in NSCLC. This study investigates exosomal mRNA expression of PD-L1 and IFN-γ, PD-L1 polymorphisms, tumor mutational load (TML) in circulating cell-free DNA (cfDNA) and radiomic features as possible predictive markers of response to nivolumab and pembrolizumab in metastatic NSCLC patients. METHODS: Patients were enrolled and blood (12 ml) was collected at baseline before receiving anti-PD-1 therapy. Exosome-derived mRNA and cfDNA were extracted to analyse PD-L1 and IFN-γ expression and tumor mutational load (TML) by digital droplet PCR (ddPCR) and next-generation sequencing (NGS), respectively. The PD-L1 single nucleotide polymorphisms (SNPs) c.-14-368 T > C and c.*395G > C, were analysed on genomic DNA by Real-Time PCR. A radiomic analysis was performed on the QUIBIM Precision® V3.0 platform. RESULTS: Thirty-eight patients were enrolled. High baseline IFN-γ was independently associated with shorter median PFS (5.6 months vs. not reached p = 0.0057), and levels of PD-L1 showed an increase at 3 months vs. baseline in patients who progressed (p = 0.01). PD-L1 baseline levels showed significant direct and inverse relationships with radiomic features. Radiomic features also inversely correlated with PD-L1 expression in tumor tissue. In subjects receiving nivolumab, median PFS was shorter in carriers of c.*395GG vs. c.*395GC/CC genotype (2.3 months vs. not reached, p = 0.041). Lastly, responders had higher non-synonymous mutations and more links between co-occurring genetic somatic mutations and ARID1A alterations as well. CONCLUSIONS: A combined multiparametric approach may provide a better understanding of the molecular determinants of response to immunotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/patologia , Mutação , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Ácidos Nucleicos Livres/análise , Ácidos Nucleicos Livres/genética , Feminino , Seguimentos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Polimorfismo Genético , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
14.
Oncoimmunology ; 9(1): 1832348, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33178494

RESUMO

Despite a proportion of renal cancer patients can experiment marked and durable responses to immune-checkpoint inhibitors, the treatment efficacy is widely variable and identifying the patient who will benefit from immunotherapy remains an issue. We performed a prospective study to investigate if soluble forms of the immune-checkpoints PD-1 (sPD-1), PD-L1 (sPD-L1), pan-BTN3As, BTN3A1, and BTN2A1, could be candidate to predict the response to immune-checkpoint blockade therapy. We evaluated the plasma levels in a learning cohort of metastatic clear cell renal carcinoma (mccRCC) patients treated with the anti-PD-1 agent nivolumab by ad hoc developed ELISA's. Using specific cut-offs determined through ROC curves, we showed that high baseline levels of sPD-1 (>2.11 ng/ml), sPD-L1 (>0.66 ng/ml), and sBTN3A1 (>6.84 ng/ml) were associated with a longer progression-free survival (PFS) to nivolumab treatment [median PFS, levels above thresholds: sPD-1, 20.7 months (p < .0001); sPD-L1, 19 months (p < .0001); sBTN3A1, 17.5 months (p = .002)]. High sPD-1 and sBTN3A1 levels were also associated with best overall response by RECIST and objective response of >20%. The results were confirmed in a validation cohort of 20 mccRCC patients. The analysis of plasma dynamic changes after nivolumab showed a statistically significant decrease of sPD-1 after 2 cycles (Day 28) in the long-responder patients. Our study revealed that the plasma levels of sPD-1, sPD-L1, and sBTN3A1 can predict response to nivolumab, discriminating responders from non-responders already at therapy baseline, with the advantages of non-invasive sample collection and real-time monitoring that allow to evaluate the dynamic changes during cancer evolution and treatment.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Antígenos CD , Antígeno B7-H1 , Butirofilinas , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Prognóstico , Receptor de Morte Celular Programada 1 , Estudos Prospectivos
15.
Ther Adv Med Oncol ; 12: 1758835920968463, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33224275

RESUMO

Background: This prospective, multicentre, observational INVIDIa-2 study is investigating the clinical efficacy of influenza vaccination in advanced-cancer patients receiving immune-checkpoint inhibitors (ICIs), enrolled in 82 Italian centres, from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until 30 April 2020. All the ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the study prospectively recorded all the COVID-19 ILI events. Patients and methods: Patients were included in this non-prespecified COVID-19 analysis, if alive on 31 January 2020, when the Italian government declared the national emergency. The prevalence of confirmed COVID-19 cases was detected as ILI episode with laboratory confirmation of SARS-CoV-2. Cases with clinical-radiological diagnosis of COVID-19 (COVID-like ILIs), were also reported. Results: Out of 1257 enrolled patients, 955 matched the inclusion criteria for this unplanned analysis. From 31 January to 30 April 2020, 66 patients had ILI: 9 of 955 cases were confirmed COVID-19 ILIs, with prevalence of 0.9% [95% confidence interval (CI): 0.3-2.4], a hospitalization rate of 100% and a mortality rate of 77.8%. Including 5 COVID-like ILIs, the overall COVID-19 prevalence was 1.5% (95% CI: 0.5-3.1), with 100% hospitalization and 64% mortality. The presence of elderly, males and comorbidities was significantly higher among patients vaccinated against influenza versus unvaccinated (p = 0.009, p < 0.0001, p < 0.0001). Overall COVID-19 prevalence was 1.2% for vaccinated (six of 482 cases, all confirmed) and 1.7% for unvaccinated (8 of 473, 3 confirmed COVID-19 and 5 COVID-like), p = 0.52. The difference remained non-significant, considering confirmed COVID-19 only (p = 0.33). Conclusion: COVID-19 has a meaningful clinical impact on the cancer-patient population receiving ICIs, with high prevalence, hospitalization and an alarming mortality rate among symptomatic cases. Influenza vaccination does not protect from SARS-CoV-2 infection.

16.
J Nephrol ; 33(6): 1143-1149, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33242211

RESUMO

Onconephrology is a rapidly evolving subspecialty that covers all areas of renal involvement in cancer patients. The complexity of the field may benefit from well-defined multidisciplinary management by a dedicated team. Patients with cancer frequently suffer from concurrent chronic kidney disease (CKD), with a prevalence ranging from 12% to 53% at the time of cancer diagnosis. Taking into account the incidence of cancer and the prevalence of CKD in the Italian population, we estimate that about 44,000 patients suffered from both diseases in 2020. Since there is an increasing necessity to address the needs of this population in dedicated outpatient clinics, it is critical to highlight some basic characteristics and to suggest areas of development. Our experience in the nephrological management of cancer patients clearly suggests the need to implement dedicated multidisciplinary teams and to create onconephrology clinics (at least within larger, referral, hospitals). Furthermore, it must be kept in mind that not only is CKD common in cancer patients, but also that the concomitant presence of these two conditions too often excludes cancer patients from clinical trials, thus limiting their access to therapies that could potentially improve their outcomes. Indeed, the Renal Insufficiency and Cancer Medications (IRMA) study found that cancer patients with CKD or on dialysis are often undertreated, or are exposed to either ineffective or toxic anticancer agents. Finally, the aim of this article is to initiate a debate about what an onconephrology outpatient clinic might look like, in order to ensure the highest quality of care for this growing patient population.


Assuntos
Neoplasias Renais , Nefrologia , Insuficiência Renal Crônica , Instituições de Assistência Ambulatorial , Humanos , Rim , Neoplasias Renais/complicações , Neoplasias Renais/diagnóstico , Neoplasias Renais/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia
17.
Expert Opin Pharmacother ; 21(18): 2199-2204, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32870051

RESUMO

INTRODUCTION: The treatment of low-grade upper tract urothelial carcinomas (UTUCs) after either surgery, or nephron-sparing techniques remains an unmet need in Genitourinary (GU) Oncology. UGN-101 is a novel drug in development for the treatment of UTUCs; it is composed of a sustained-release hydrogel polymer-based formulation containing the antitumor antibiotic mitomycin-C (MM-C); cold UGN-101 is liquid, but at body temperature, it becomes a gel, and thus, when administered through a ureteral catheter, it sticks to the upper tract urothelium, slowly releasing MM-C. AREAS COVERED: Here, the authors review the preclinical rationale for the development of UGN-101, as well as presently available clinical results for the treatment of low-grade UTUCs. EXPERT OPINION: The positive results of the recently completed OLYMPUS trial suggest the feasibility, activity (59% of complete responses, with just 6 of these complete responders on follow-up who recurred), and safety (68% of patients experiencing mild to moderate urinary adverse events) of UGN-101 instillations into the upper urinary tract. Our expectations are that UGN-101 will soon become a standard of treatment for low-grade UTUC at risk of relapse after either surgery, or nephron-sparing techniques.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Carcinoma de Células de Transição/tratamento farmacológico , Hidrogéis/química , Mitomicina/farmacologia , Polímeros/química , Neoplasias Urológicas/tratamento farmacológico , Urotélio/patologia , Antibióticos Antineoplásicos/química , Carcinoma de Células de Transição/patologia , Ensaios Clínicos como Assunto , Preparações de Ação Retardada , Desenvolvimento de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos , Mitomicina/química , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Urológicas/patologia
18.
Expert Opin Drug Saf ; 19(10): 1329-1338, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32799582

RESUMO

INTRODUCTION: Immune-based combinations, including nivolumab plus ipilimumab, pembrolizumab plus axitinib, and (at a lesser extent) avelumab plus axitinib, should be regarded among the new standards of care for first line therapy of metastatic renal cell carcinoma. Toxicity profiles are different among all these above combinations, as well as between them and targeted agents monotherapies, including sunitinib (i.e. the control arm of all the above studies). AREAS COVERED: We performed a systematic review and meta-analysis with the aim to compare adverse events from immune-based combinations versus sunitinib monotherapy across four recent randomized controlled trials (CheckMate-214, Keynote-426, IMmotion-151, and JAVELIN Renal 101) of front-line treatment for metastatic renal cell carcinoma, with particular attention to those from the ipilimumab plus nivolumab combination. EXPERT OPINION: Beyond efficacy and activity, the ipilimumab plus nivolumab combination appears feasible, being endowed by an acceptable safety profile, in line with that of the other available options for the treatment of metastatic RCC. The different patterns of toxicities emerging from this systematic review and meta-analysis need to be kept in mind while choosing the appropriate treatment for each individual patient. Furthermore, prevention, prompt identification, and treatment of immune-related adverse events remains an area to be improved.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Terapia de Alvo Molecular , Metástase Neoplásica , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Crit Rev Oncol Hematol ; 154: 102891, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32340783

RESUMO

Chemotherapy is the reference treatment for patients with advanced urothelial carcinoma, both in the neo-adjuvant and adjuvant settings; however, the overall outcome remains poor in this patient population. In the last few years, the addition of immune checkpoint inhibitors into the therapeutic armamentarium has changed the therapeutic landscape of several tumor types, including urothelial carcinoma. Many different molecules have been introduced in the clinical use and several questions about immunotherapies are currently open and deserve a critical analysis. The current review article is aimed at describing the clinical pharmacology of monoclonal antibodies targeting PD-1 axis in urothelial malignancies to underline pharmacodynamic and pharmacokinetic differences among them.

20.
Crit Rev Oncol Hematol ; 144: 102812, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31698313

RESUMO

Chemotherapy is the reference treatment for patients with advanced urothelial carcinoma, both in the neo-adjuvant and adjuvant settings; however, the overall outcome remains poor in this patient population. In the last few years, the addition of immune checkpoint inhibitors into the therapeutic armamentarium has changed the therapeutic landscape of several tumor types, including urothelial carcinoma. Many different molecules have been introduced on the market and several questions about immunotherapies are currently open and deserve a critical analysis. The current review article is aimed at describing the clinical pharmacology of monoclonal antibodies targeting PD-1 axis in urothelial malignancies to underline possible pharmacodynamic and pharmacokinetic differences among them.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Receptor de Morte Celular Programada 1 , Neoplasias da Bexiga Urinária , Antígeno B7-H1 , Carcinoma de Células de Transição , Humanos , Imunoterapia
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