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1.
Immunotherapy ; 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34784782

RESUMO

Background: Few data are available regarding the effectiveness of immune checkpoint inhibitors in advanced upper tract urothelial carcinoma (UTUC) patients. Methods: To provide a real-world experience with anti-PD-1/PD-L1-based therapy in UTUC patients, we involved an Italian network in a multicenter retrospective analysis. Results: A total of 78 UTUC patients were enrolled. The median follow-up was 25.1 months. The median progression-free survival (mPFS) was 2.2 months (95% CI 1.8-2.6), and the median OS (mOS) was 6.0 months (95% CI 3.6-8.4). The Sonpavde score (including performance status > 0, hemoglobin < 10 g/dl, liver metastases, time from prior chemotherapy ≥ 3 months) split the patients into three groups (0 vs 1 vs 2-4 factors), efficiently predicting the OS and PFS outcome at the multivariate analyses (p < 0.0001). Conclusion: The prognosis of unselected UTUC patients is still unsatisfactory. The Sonpavde score was validated for the first time in an UTUC population, as a useful tool for the treatment decision-making process.

2.
Front Oncol ; 11: 682449, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168997

RESUMO

Background: Immune-Oncology (IO) improves Overall Survival (OS) in metastatic Renal Cell Carcinoma (mRCC). The prognostic impact of previous Cytoreductive Nephrectomy (CN) and radical nephrectomy (RN), with curative intent, in patients treated with IO is not well defined. The aim of our paper is to evaluate the impact of previous nephrectomy on outcome of mRCC patients treated with IO. Methods: 287 eligible patients were retrospectively collected from 16 Italian referral centers adhering to the MeetUro association. Patients treated with IO as second and third line were included, whereas patients treated with IO as first line were excluded. Kaplan-Meier method and log-rank test were performed to compare Progression Free Survival (PFS) and OS between groups. In our analysis, both CN and RN were included. The association between nephrectomy and other variables was analyzed in univariate and multivariate setting using the Cox proportional hazard model. Results: 246/287 (85.7%) patients had nephrectomy before IO treatment. Median PFS in patients who underwent nephrectomy (246/287) was 4.8 months (95%CI 3.9-5.7) vs 3.7 months (95%CI 1.9-5.5) in patients who did not it (HR log rank 0.78; 95%CI 0.53 to 1.15; p = 0.186). Median OS in patients who had previous nephrectomy (246/287) was 20.9 months (95%CI 17.6-24.1) vs 13 months (95%CI 7.7-18.2) in patients who did not it (HR log rank 0.504; 95%CI 0.337 to 0.755; p = 0.001). In the multivariate model, nephrectomy showed a significant association with OS (HR log rank 0.638; 95%CI 0.416 to 0.980), whereas gland metastases were still associated with better outcome in terms of both OS (HR log rank 0.487; 95%CI 0.279 to 0.852) and PFS (HR log rank 0.646; 95%CI 0.435 to 0.958). Conclusions: IO treatment, in patients who had previously undergone nephrectomy, was associated with a better outcome in terms of OS. Further prospective trials would assess this issue in order to guide clinicians in real word practice.

3.
Ther Adv Med Oncol ; 13: 17588359211019642, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046089

RESUMO

Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need. Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites. Results: From October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS - mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups. Conclusion: The Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations.

4.
Minerva Urol Nephrol ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33781017

RESUMO

BACKGROUND: Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are markers of systemic inflammation associated with poor outcome in several solid tumours. We retrospectively investigated the prognostic role of PLR and, secondly, NLR in mCRPC patients treated with Abiraterone Acetate (AA) or Enzalutamide (E), both in pre- and post-docetaxel setting. MATERIALS AND METHODS: 225 mCRPC patients treated with AA or E with basal blood count were divided in three groups according to PLR (PLR1 <128; PLR2 128-190; PLR >190) and in two groups according to NLR (<3 vs ≥3). Outcome measures were progression-free survival (PFS) and overall-survival (OS). Univariate and multivariate analyses were performed. RESULTS: 110 patients were in PLR1, 58 in PLR2 and 57 in PLR3. Median OS was 22.0, 20.6 and 21.2 months in PLR1, PLR2 and PLR3 (PLR2 vs PLR1: HR 0.97, 95%CI 0.62-1.52, p=0.90; PLR3 vs PLR1: HR 1.37, 95%CI 0.90-2.08, p=0.14). Median PFS was 9.2, 12.7 and 8.5 months in PLR1, PLR2 and PLR3 (PLR2 vs PLR1: HR 0.87, 95%CI 0.59-1.27, p=0.47; PLR3 vs PLR1: HR 1.15, 95%CI 0.80-1.66, p=0.45). 142 patients were in NLR<3 and 83 in NLR≥3. Median OS was 26.5 months in NLR<3 and 17.0 months in NLR≥3 (HR 1.75, 95%CI 1.22-2.51, p=0.02). Median PFS was 10.1 months in NLR<3 and 7.6 months in NLR≥3 (HR 1.37, 95%CI 1.00-1.88, p=0.05). CONCLUSIONS: In this retrospective analysis of mCRPC patients treated with AA or E we did not identify a prognostic role of baseline PLR, while we found a significant prognostic role of baseline NLR.

5.
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
6.
Prostate Cancer Prostatic Dis ; 24(3): 812-825, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33603237

RESUMO

BACKGROUND: Our retrospective study aims to evaluate the prognostic role of duration of response to androgen deprivation therapy (ADT) in metastatic castration resistant prostate cancer (mCRPC) patients treated with enzalutamide (E) or abiraterone acetate (AA). MATERIALS AND METHODS: Data about ADT start and duration were available in 255 (82%) of 311 patients treated with AA or E. Patients were divided in three groups according to ADT response (group 1 [G1]: <12 months; group 2 [G2]: 12-36 months; group 3 [G3]: >36 months). Outcome measures were progression-free survival (PFS) and overall survival (OS). RESULTS: Patients with longer ADT response had better OS (median 17.3 months G1, 19.9 months G2, 31.6 months G3; HR G3 vs G1 0.41, 95% CI 0.25-0.64; p = 0.001) and better PFS (median 5.9 months G1, 8.8 months G2, 11.7 months G3; HR G3 vs G1 0.41, 95% CI 0.41-0.27; p < 0001). In docetaxel-naive patients, median OS was 18.8 in G1, 35.2 in G2, and not reached in G3 (HR G3 vs G1 0.33, 95% CI 0.14-0.78; p = 0.038), median PFS was 7 months G1, 9.3 months G2, and 20 months G3 (HR G3 vs G1 0.31, 95% CI 0.15-0.62; p = 0.003). In postdocetaxel patients, median OS was 13.1 months in G1, 17.2 months in G2, and 21.4 months in G3 (HR G3 vs G1 0.52, 95% CI 0.29-0.94; p = 0.082), while median PFS was 5.2 months in G1, 6.8 months in G2, and 8.3 months in G3 (HR G3 vs G1 0.54, 95% CI 0.32-0.91; p = 0.067). CONCLUSIONS: Duration of ADT response is an independent prognostic factor of outcome with AA or E.

7.
Artigo em Inglês | MEDLINE | ID: mdl-35000876

RESUMO

BACKGROUND: Considerable numbers of patients with metastatic urothelial carcinoma (mUC) develop bone metastases (BoM). Their impact on the efficacy of immune-checkpoint inhibitors (ICIs) is not yet investigated. METHODS: Between July 2014 and August 2020 data on pts treated with single-agent ICIs after failure of at least 1 previous line of chemotherapy for advanced disease, were retrospectively collected across 14 Italian centers. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Cox regression analysis was performed evaluating potential prognostic factors for OS and PFS. Each factor was evaluated in univariable (UVA) and multivariable analysis (MVA). RESULTS: A total of 208 evaluable patients treated with ICIs were identified, including 122 (59%) without BoM (BoM-) and 86 (41%) with bone metastases (BoM+). After a median follow-up of 22.3 months, BoM+ patients showed shorter OS (median 3.9 vs 7.8 months, HR 1.59 [95%CI, 1.15-2.20], P = .005) and shorter PFS (median 2.0 vs 2.6 months, HR 1.76 [95%CI, 1.31-2.37], P < .001). Probability of being alive was 62% vs 40% after 6 months, 38% vs 23% after 1 year and 24% vs 13% after 2 years, in BoM- and BoM+ respectively. Within each Bellmunt score, OS and PFS of BoM+ patients were shorter. Both presence of BoM and higher Bellmunt risk score were significantly associated with shorter OS and PFS in UVA and MVA. CONCLUSION: Patients treated with single-agent ICIs for BoM+ mUC have a dismal prognosis compared to BoM-. Further research is needed to understand the mechanism behind these outcomes.

8.
Recenti Prog Med ; 111(12): 740-748, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33362171

RESUMO

PURPOSE: Medical records are a relevant source for real-world evidence. We introduced patient-reported outcomes (PROs) in clinical practice, demonstrating a significant quality-of-life improvement, compared to usual visit. In this secondary analysis, we describe the agreement between patients' and physicians' reports of 5 symptoms. Our hypothesis was that adoption of PROs questionnaire could significantly improve the agreement. METHODS: Eligible patients were receiving active anti-cancer treatment. Patients in the control group underwent usual visits (group A), while patients of group B, before each visit, filled a PROs paper questionnaire, to provide information about symptoms and toxicities. No specific instructions were provided to physicians to integrate such information in medical records. Agreement between patient and physician evaluations was assessed by Cohen's κ, calculating under-reporting as proportion of toxicities reported by patients but not recorded by physicians. RESULTS: 211 patients (412 visits) have been analyzed. For all symptoms, Cohen's κ was better for group B: emesis (0.25 group A vs. 0.36 group B), diarrhea (0.16 vs. 0.57), constipation (0.07 vs. 0.28), pain (0.22 vs. 0.42), fatigue (0.03 vs. 0.08). For all symptoms, although under-reporting was relevant in both groups, it was lower for group B: emesis (75.49% vs. 60.0%, p=0.031), diarrhea (82.89% vs. 50.0%, p<0.001), constipation (92.11% vs. 69.57%, p<0.001), pain (59.57% vs. 42.31%, p=0.01), fatigue (82.11% vs. 64.10%, p<0.001). CONCLUSION: Adoption of paper PROs allowed a significant reduction in under-reporting of symptoms, but agreement remained suboptimal. Direct integration of electronic PROs could minimize the issue of under-reporting of medical records, increasing their accuracy.

9.
Cancers (Basel) ; 12(9)2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32916886

RESUMO

In patients with prostate cancer, earlier use and longer duration of new-generation hormonal therapy (NGHT), added to androgen deprivation therapy, requires careful evaluation of cognitive function. The aim of this systematic review is to describe the evidence about cognitive function in all the randomized trials (RCTs) testing NGHT (abiraterone, enzalutamide, apalutamide, darolutamide). We assessed the availability of both investigator-assessed cognitive impairment and disorders and patient-reported evaluation of cognitive function. Nineteen RCTs (17,617 patients) were included. The investigator-based evaluation of cognitive impairment was available in seven RCTs (36.8%). In total, 19/19 RCTs (100%) included patient-reported outcomes (PROs) collection, but PRO tools adopted allowed evaluation of cognitive function in two RCTs (10.5%). Among them, PRO-based cognitive function results were presented only in one RCT (5.3%): in ENZAMET, mean changes from baseline were worse with enzalutamide than with placebo, but deterioration-free survival favored enzalutamide. Despite cognitive deterioration could be relevant, clinical development of NGHT has not included a systematic evaluation of cognitive function. Assessment by investigators is at risk of underreporting, and commonly used PROs do not allow proper cognitive function analysis. Furthermore, the methodology of analysis can jeopardize the interpretation of results. Although direct comparisons are scanty, there could be differences between different NGHTs.

10.
Crit Rev Oncol Hematol ; 152: 102994, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32480269

RESUMO

Testosterone suppression by androgen deprivation therapy is the cornerstone of prostate cancer treatment. New-generation hormone therapies improved overall survival in castration-resistant prostate cancer. More recent trials showed a further increase in overall survival when enzalutamide or abiraterone are associated with androgen deprivation therapy in hormone-sensitive disease. However, a higher clonal pressure may lead to the upregulation of alternative pathways for cancer progression and to dedifferentiated diseases that would probably respond poorly to subsequent treatments. In this contest, new strategies that could be able to delay or even revert resistance are needed. The bipolar androgen therapy is an under-investigation treatment that consists in periodical oscillation between castration levels and supraphysiological levels of testosterone in order to prevent the adaptation of prostate cancer cells to a low-androgen environment. This review aims to underline the biological rationale of bipolar androgen therapy and gather evidences from the most recent clinical trials.


Assuntos
Neoplasias da Próstata/tratamento farmacológico , Antagonistas de Androgênios , Androgênios , Humanos , Masculino , Orquiectomia , Receptores Androgênicos
11.
Minerva Urol Nefrol ; 72(6): 737-745, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32284527

RESUMO

BACKGROUND: Previous studies demonstrated a predictive value of prostate-specific antigen (PSA) kinetics for treatment outcome. Our retrospective study evaluates the prognostic role of early PSA drop in metastatic castration resistant prostate cancer (mCRPC) patients receiving abiraterone acetate (AA) or enzalutamide (E). METHODS: All mCRPC patients treated with AA or E at the San Luigi Hospital in Orbassano between 2010 and 2018 and at the Ordine Mauriziano Hospital in Turin between 2014 and 2018 were included in this retrospective study. Only patients with an early PSA (measured 28-60 days after the beginning of the treatment) were included in the analysis. Patients were divided in early responders and non-early responders according to early PSA response (drop≥50% from baseline). Univariate and multivariate analyses for progression free survival (PFS) and overall survival (OS) were performed. RESULTS: Of 144 patients with early PSA value, 61 (42.4%) patients received E (docetaxel-naïve 42, post-docetaxel 19) and 83 (57.6%) received AA (docetaxel-naïve 44, post-docetaxel 39). Seventy-five (52.1%) patients achieved early PSA drop. In docetaxel-naïve setting (N.=86), median PFS was 14.9 (with early PSA drop) vs. 8.8 months (without early PSA drop, P=0.001). In post-docetaxel setting (N.=58) median PFS was 11.9 vs. 4.5 months (P<0.001). Globally, median PFS was 14.9 vs. 6.3 months in patients with and without early PSA drop, respectively (P<0.001). In docetaxel-naïve setting, patients with early PSA drop had a median OS of 39.5 vs. 18.8 months (P=0.12). In post-docetaxel setting median OS was 29.6 vs. 10.7 months (P=0.01). Comprehensively, median OS was 31.9 vs. 16.3 (P=0.002) in patients with and without early PSA drop, respectively. At multivariate analysis, early PSA drop confirmed an independent association with PFS (HR 0.21; 95% CI: 0.12-0.38, P<0.001) and OS (HR 0.25; 95% CI: 0.12-0.50, P<0.001). CONCLUSIONS: mCRPC patients treated with AA or E, in docetaxel-naïve or post-docetaxel setting, with early PSA drop had significantly better OS and PFS.


Assuntos
Acetato de Abiraterona , Antineoplásicos , Feniltioidantoína/análogos & derivados , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração , Acetato de Abiraterona/uso terapêutico , Idoso , Antineoplásicos/uso terapêutico , Benzamidas , Intervalo Livre de Doença , Docetaxel/uso terapêutico , Humanos , Calicreínas , Masculino , Pessoa de Meia-Idade , Nitrilas , Feniltioidantoína/uso terapêutico , Prognóstico , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Resultado do Tratamento
12.
Support Care Cancer ; 27(12): 4697-4704, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30949832

RESUMO

INTRODUCTION: Patient-reported outcomes (PROs) are the gold standard to describe subjective symptoms. Nurses can be successfully involved in collecting symptom information, because of their direct relationship with the patient. In order to improve clinical management of outpatients receiving active anti-cancer treatment, we introduced in routine clinical practice an assessment of patient-reported symptoms and toxicities, starting from January 2018. Our hypothesis was that this could help to better control symptoms, improving patients' quality of life (QoL). METHODS: Eligible patients were receiving an active anti-cancer treatment, as outpatients. Patients included in the control group (treated in 2017) underwent "usual" visits (group A), while patients treated in 2018, before each visit received a questionnaire by a dedicated nurse, in order to provide information about symptoms and toxicities (group B). Primary objective was the comparison of QoL changes, measured by EORTC QLQ-C30. RESULTS: A total of 211 patients have been analyzed (119 group A; 92 group B). After 1 month, mean change from baseline of global QoL was - 1.68 in group A and + 2.54 in group B (p = 0.004, effect size 0.20). Group B showed significantly better mean changes for fatigue, pain, and appetite loss. Proportion of patients obtaining a clinically significant improvement in global QoL score was higher in group B (32.6%) compared to group A (19.3%, p = 0.04). Patients' satisfaction with questionnaire was high. CONCLUSION: Introduction of PROs in clinical practice, thanks to an active role of nurses, was feasible, produced high patients' satisfaction and a significant QoL improvement, compared to the traditional modality of visit.


Assuntos
Neoplasias/diagnóstico , Neoplasias/terapia , Medidas de Resultados Relatados pelo Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anorexia/etiologia , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/fisiopatologia , Neoplasias/psicologia , Papel do Profissional de Enfermagem , Pacientes Ambulatoriais , Dor/etiologia , Qualidade de Vida , Inquéritos e Questionários
13.
Clin Genitourin Cancer ; 17(1): e150-e155, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30396828

RESUMO

BACKGROUND: Pazopanib has been approved for first-line treatment of patients with metastatic renal-cell carcinoma on the basis of clinical trials that enrolled only patients with adequate renal function. Few data are available on the safety and efficacy of pazopanib in patients with renal insufficiency. This study investigated the effect of kidney function on treatment outcomes in such patients. PATIENTS AND METHODS: We retrospectively analyzed data of metastatic renal-cell carcinoma patients treated with pazopanib from January 2010 to June 2016 with respect to renal function. Patients with Modification of Diet in Renal Disease ≤ 60 mL/min/1.73 m2 (group A) were compared to patients with Modification of Diet in Renal Disease > 60 mL/min/1.73 m2 (group B) in terms of progression-free survival, toxicities, response rates, and overall survival. RESULTS: A total of 229 patients were included: 128 in group A and 101 in group B. Median progression-free survival was 14 months (95% confidence interval [CI], 9.4-18.5) and 17 months (95% CI, 11.4-22.8), and overall survival was 30.5 months (95% CI, 8-53) and 41.4 months (95% CI, 21-62) for group A and group B, respectively, with no significant difference (P = .6). No significant difference between the 2 groups was reported in the incidence of adverse events. Dose reductions were more frequent in group A patients (66% vs. 36%; P = .04). CONCLUSION: Although the dose of pazopanib was reduced more frequently in patients with renal impairment, kidney function at therapy initiation does not adversely affect the safety and efficacy of pazopanib.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Pirimidinas/uso terapêutico , Insuficiência Renal/complicações , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/secundário , Feminino , Seguimentos , Humanos , Indazóis , Neoplasias Renais/etiologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
14.
Onco Targets Ther ; 11: 7353-7368, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30425524

RESUMO

The new-generation hormonal agent enzalutamide has been approved for the treatment of metastatic castration-resistant prostate cancer (CRPC), in both post- and predocetaxel setting, due to the significant improvement in overall survival. More recently, enzalutamide also showed impressive results in the treatment of men with nonmetastatic CRPC. Unfortunately, not all patients with CRPC are responsive to enzalutamide, and even in responders, benefits are limited by the development of drug resistance. Adaptive resistance of metastatic prostate cancer to enzalutamide treatment can be due to the activation of both androgen receptor (AR)-dependent pathways (expression of constitutively active AR splice variants, AR point mutations, gene amplification and overexpression) and mechanisms independent of AR signaling pathway (altered steroidogenesis, upregulation of the glucocorticoid receptor, epithelial-mesenchymal transition, neuroendocrine transformation, autophagy and activation of the immune system). In this review, we focus on resistance mechanisms to enzalutamide, exploring how we could overcome them through novel therapeutic options.

15.
Crit Rev Oncol Hematol ; 129: 124-132, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30097230

RESUMO

Immunotherapy represents a new hope for patients with advanced urothelial carcinoma (UC). However, to date, only one of two randomized studies showed a clear survival advantage with these treatments. Aimed to investigate the role of immune-checkpoint inhibitors in patients with platinum progressed metastatic UC we performed a systematic review and meta-analysis of clinical trials to evaluate the efficacy and activity, in terms of Overall Survival (OS) and Objective Response Rate (ORR). Immune checkpoint inhibitors have showed to improve OS compared to chemotherapy in unselected patients (HR 0.80, 95% CI 0.69-0.93, p = 0.003), while the difference was not significant in patients selected for PD-L1 expression (HR 0.72, 95% CI 0.48-1.09, p = 0.12). Pooled probability of response was 0.18 (95% CI 0.16-0.20) in unselected patients and 0.27 (95% CI 0.25-0.32) in PD-L1 selected patients. Immunotherapy results in a significant survival advantage in PD-L1 unselected patients suggesting that PD-L1 expression may not be a reliable marker in previously platinum treated patients.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores , Imunoterapia/métodos , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/secundário , Humanos
17.
Clin Genitourin Cancer ; 16(4): 318-324, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29866495

RESUMO

BACKGROUND: Neutropenia is a common side effect associated with docetaxel use. We retrospectively investigated the association between chemotherapy-induced neutropenia and survival in metastatic castration-resistant prostate cancer (mCRPC) patients receiving first-line docetaxel. PATIENTS AND METHODS: Metastatic castration-resistant prostate cancer patients treated with first-line docetaxel, with known neutrophils value 10 days after first administration, were included in this retrospective analysis. Neutropenia was categorized in Grade 0 to 1 (G0-1), Grade 2 to 3 (G2-3), and Grade 4 (G4). Outcome measures were progression-free survival (PFS) and overall survival (OS). RESULTS: Eighty patients were analyzed. Median PFS was 5.4 months in patients with G0-1 neutropenia, 6.9 months with G2-3 neutropenia (hazard ratio [HR] vs. G0-1, 0.69; 95% confidence interval [CI], 0.35-1.35; P = .27) and 9.5 months with G4 neutropenia (HR vs. G0-1, 0.30; 95% CI, 0.16-0.57; P < .0001). Median OS was 11.6 months in patients with G0-1 neutropenia, 25.5 months in patients with G2-3 neutropenia (HR vs. G0-1, 0.36; 95% CI, 0.16-0.80; P = .012) and 39.3 months in patients with G4 neutropenia (HR vs. G0-1, 0.19; 95% CI, 0.09-0.41; P < .0001). In multivariate analysis, the occurrence of severe neutropenia showed a statistically significant association with OS (HR G4 vs. G0-1, 0.14; 95% CI, 0.03-0.67; P = .013; HR G2-3 vs. G0-1, 0.42; 95% CI, 0.11-1.57; P = .20) and PFS (HR G4 vs. G0-1, 0.28; 95% CI, 0.09-0.86; P = .03; HR G2-3 vs. G0-1, 1.07; 95% CI, 0.38-2.96; P = .90). CONCLUSION: Docetaxel-induced neutropenia is associated with better survival of mCRPC.


Assuntos
Antineoplásicos/administração & dosagem , Docetaxel/administração & dosagem , Neutropenia/induzido quimicamente , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Contagem de Células Sanguíneas , Docetaxel/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Intervalo Livre de Progressão , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
18.
Crit Rev Oncol Hematol ; 124: 21-28, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29548482

RESUMO

According to current ESMO - MASCC guidelines, a combination of a neurokinin-1 receptor antagonist (NK1RA), dexamethasone and a 5-HT3 receptor antagonist (5-HT3RA) is recommended to prevent carboplatin-induced emesis, albeit with moderate level of confidence and not unanimous consensus. We performed a meta-analysis of randomized trials (RCTs) comparing NK1RA + dexamethasone + 5-HT3RA vs. dexamethasone + 5-HT3RA in patients receiving the first cycle of carboplatin-based chemotherapy. Primary outcome was complete response (CR), defined as no emesis and no use of rescue medication. 9 trials were eligible, and data of CR were available from 8 trials (1598 patients). Addition of NK1RA improves CR in all phases: acute phase, 94.5% vs. 90.1%; delayed phase, 76.4% vs. 61.7%; overall period, 75.3% vs. 60.4%. There was no significant heterogeneity among trials. In patients receiving carboplatin-based chemotherapy, the addition of NK1RA to dexamethasone and 5-HT3RA is associated with a statistically significant and clinically relevant improvement in CR.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Náusea/induzido quimicamente , Náusea/prevenção & controle , Antagonistas dos Receptores de Neurocinina-1/uso terapêutico , Vômito/induzido quimicamente , Vômito/prevenção & controle , Antieméticos/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Humanos , Resultado do Tratamento
19.
Minerva Urol Nefrol ; 70(2): 144-151, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29241313

RESUMO

Androgen deprivation therapy (ADT) is the mainstay of treatment of patients with relapsed or metastatic hormone-sensitive prostatic carcinoma. The dramatic reduction of serum testosterone levels induced by ADT produces multiple side effects as vasomotor flushing, sexual dysfunction, fatigue, impairment of cognitive function, reduced quality of sleep, gynecomastia and anemia, that are able to decrease health-related quality of life (QoL). In addition, hormonal therapy can interfere with bone metabolism and induce metabolic and cardiovascular complications. Recently, new-generation hormonal therapies, such as abiraterone and enzalutamide, have been tested and approved in castration resistant prostatic cancer patients and current studies are moving forward to the earlier use of these two drugs. In this evolving scenario, the management of hormonal therapy toxicity, given the long duration of treatment and the potentially high impact of side effects on patients' functional status and quality of life, is a critical challenge for clinicians. A correct information of patients before the initiation of treatment, together with the adoption of preventive measures, could help to ameliorate their quality of life. The aim of this review is to describe the impact on quality of life of endocrine treatment side effects and analyze possible interventions to alleviate them.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Hormônios/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/psicologia , Medicina Baseada em Evidências , Humanos , Masculino , Orquiectomia/efeitos adversos , Neoplasias de Próstata Resistentes à Castração , Qualidade de Vida
20.
Endocr Relat Cancer ; 25(1): R1-R9, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28971898

RESUMO

Antiandrogen withdrawal syndrome is an unpredictable event diagnosed in patients with hormone-sensitive prostate cancer treated with combined androgen blockade therapy. It is defined by prostate-specific antigen value reduction, occasionally associated with a radiological response, that occurs 4-6 weeks after first-generation antiandrogen therapy discontinuation. New-generation hormonal therapies, such as enzalutamide and abiraterone acetate, improved the overall survival in patients with metastatic castration-resistant prostate cancer, and recent trials have also shown the efficacy of abiraterone in hormone-sensitive disease. In the last few years, several case reports and retrospective studies suggested that the withdrawal syndrome may also occur with these new drugs. This review summarizes literature data and hypothesis about the biological rationale underlying the syndrome and its potential clinical relevance, focusing mainly on new-generation hormonal therapies. Several in vitro studies suggest that androgen receptor gain-of-function mutations are involved in this syndrome, shifting the antiandrogen activity from antagonist to agonist. Several different drug-specific point mutations have been reported. The association of the withdrawal syndrome for enzalutamide and abiraterone needs confirmation by additional investigations. However, new-generation hormonal therapies being increasingly used in all stages of disease, more patients may experience the syndrome when stopping the treatment at the time of disease progression, although the clinical relevance of this phenomenon in the management of metastatic castration-resistant prostate cancer remains to be defined.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Receptores Androgênicos/química , Síndrome de Abstinência a Substâncias/etiologia , Humanos , Masculino
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